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Study of Safety and Drug Levels of CCI15106 Inhalation Powder in Healthy Adults and Adults With Moderate Chronic Obstructive Pulmonary Disease. Study of CCI15106 Levels in People Standing Near the Person Inhaling the Drug

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

CCI15106

Placebo

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring bystander, inhalation powder, monodose device, COPD, pharmacokinetics, safety, Healthy, CCI15106, tolerability

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Some important Inclusion Criteria:

For healthy subjects and bystanders:

18 to 65 years of age.
Healthy as determined by a doctor.
Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period.
Women who are not pregnant or breastfeeding, and not of childbearing potential.

For subjects with COPD:

40 to 75 years of age.
Diagnosed with moderate COPD by a doctor.
Have breathing test results that are consistent with moderate COPD as defined in the study protocol.
A smoker or an ex-smoker.
Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period.
Women who are not pregnant or breastfeeding, and not of childbearing potential.

Some Important Exclusion Criteria:

For healthy subjects and bystanders:

History of liver disease.
Use of over-the-counter or prescription drugs (including vitamins) 7 days before the study until completion of the follow-up visit.
Participation in the study would result in loss of more than 500 milliliter (mL) of blood within 3 months.
Participation in another clinical trial with an investigational product within about 3 months before this study.
Positive drug/alcohol screen.
Regular use of known drugs of abuse.
Regular alcohol consumption within 3 months before the study.
Breath test indicative of smoking at study start.
Documented lactose allergy/intolerance.
Men whose partner is pregnant or breastfeeding cannot participate.
Certain blood test results may not allow subjects to participate, as described in the study protocol.

For subjects with COPD:

History of liver disease.
Poorly controlled COPD disease as, for example, more than 2 exacerbations of COPD per year.
Some respiratory conditions, like for example active tuberculosis, lung cancer or any other respiratory condition. Subjects with other respiratory conditions (for example, clinically significant: asthma, pulmonary fibrosis, bronchiectasis) are excluded if these conditions are the primary cause of their respiratory symptoms.
Unstable or uncontrolled cardiac disease.
Problems with kidney function as defined in the study protocol.
Past or current medical conditions or diseases that are not well controlled.
Subjects are not allowed to take oral corticosteroids from 4 weeks prior to screening and for the duration of the study.
Subjects taking medications for any chronic conditions have to be on stable doses for 4 weeks before screening and until after study treatment is finished.
Use of short-acting inhaled bronchodilators is allowed, but subjects must be able to stop their medications several times during the study.
Use of long-acting bronchodilators is allowed, but subjects must be able to change the schedule of their medications twice during the study.
Participation in the study would result in loss of more than 500 mL within 3 months.
Participation in another clinical trial with an investigational product within about 3 months before this study.
Positive drug/alcohol screen.
Regular use of known drugs of abuse.
Regular alcohol consumption within 3 months before the study.
Unable to refrain from smoking for certain periods during the study (maximum about 6 hours).
Documented lactose allergy/intolerance.
Men whose partner is pregnant or breastfeeding cannot participate.
Certain blood test results may not allow subjects to participate, as described in the study protocol.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

No Intervention

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Cohort A, Part 1: Active

Cohort A, Part 1: Placebo

Cohort B, Part 1: Active

Cohort B, Part 1: Placebo

Cohort C, Part 1: bystanders

Cohort A, Part 2: Active

Cohort A, Part 2: Placebo

Cohort B, Part 2: Active

Cohort B, Part 2: Placebo

Arm Description

60 milligrams (mg) single dose of CCI15106 will be administered by inhalation route on Day 1; 120 mg single dose will be administered on Day 3; and then 30 mg dose will be administered twice daily (BID) on Days 6-19 to healthy subjects.

60 mg single dose of placebo will be administered by inhalation route on Day 1; 120 mg single dose will be administered on Day 3; and then 30 mg dose will be administered BID on Days 6-19 to healthy subjects.

60 mg of CCI15106 BID will be administered by inhalation route for 14 days to healthy subjects.

60 mg of placebo BID will be administered by inhalation route for 14 days to healthy subjects.

Healthy subjects will be enrolled to follow bystander exposure and will be studied concomitantly with Cohort B.

60 mg single dose of CCI15106 will be administered by inhalation route to subjects with COPD.

60 mg single dose of placebo will be administered by inhalation route to subjects with COPD.

60 mg BID dose of CCI15106 will be administered by inhalation route for 14 days to subjects with COPD.

60 mg BID dose of placebo will be administered by inhalation route for 14 days to subjects with COPD.

Outcomes

Primary Outcome Measures

Part 1 Cohort A: Number of Participants With Non-serious Adverse Events (NSAEs) and Serious Adverse Events (SAEs) in CCI15106

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician. Safety population comprised of all participants who received at least one dose of study treatment during the study.

Part 1 Cohort B: Number of Participants With NSAEs and SAEs in CCI15106

Part 1 Cohort C: Number of Participants With NSAEs and SAEs in Bystanders

Part 2 Cohort A: Number of Participants With NSAEs and SAEs

Part 2 Cohort B: Number of Participants With NSAEs and SAEs

Part 1: Number of Participants With Hematology Values of Potential Clinical Importance (PCI) in CCI15106

PCI ranges for the hematology parameters were as follows: hematocrit (high: >0.54 proportion of red blood cell [RBC] in blood for male, >0.54 proportion of RBC in blood for female), hemoglobin (high: >180 grams [g]/L in male, >180 g/L in female), lymphocytes (low: <0.8 10^9/L), neutrophil count (low: <1.5 10^9/L) and platelet count (low: <100 10^9/L and high: 550 10^9/L). Data for the participants with high and low values has been reported.

Part 1: Number of Participants With Hematology Values of PCI in Bystanders

PCI ranges for the hematology parameters were as follows: hematocrit (high: >0.54 proportion of RBC in blood for male, >0.54 proportion of RBC in blood for female), hemoglobin (high: >180 g/L in male, >180 g/L in female), lymphocytes (low: <0.8 10^9/L), neutrophil count (low: <1.5 10^9/L) and platelet count (low: <100 10^9/L and high: 550 10^9/L). Data for the participants with high and low values has been reported.

Part 2: Number of Participants With Hematology Values of PCI

Part 1: Number of Participants With Clinical Chemistry Values of PCI in CCI15106

PCI ranges for the clinical chemistry parameters were as follows: albumin (low: <30 millimole per liter [mmol/L]), calcium (low: <2 mmol/L and high: >2.75 mmol/L), glucose (low: <3 mmol/L and high: >9 mmol/L), potassium (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L). Data for the participants with high and low values has been reported.

Part 1: Number of Participants With Clinical Chemistry Values of PCI in Bystanders

PCI ranges for the clinical chemistry parameters were as follows: albumin (low: <30 mmol/L), calcium (low: <2 mmol/L and high: >2.75 mmol/L), glucose (low: <3 mmol/L and high: >9 mmol/L), potassium (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L). Data for the participants with high and low values has been reported.

Part 2: Number of Participants With Clinical Chemistry Values of PCI

Part 1 Cohort A: Potential of Hydrogen (pH) Value by Visit- CCI15106 60 mg SD

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 1 Cohort A: pH Value by Visit- CCI15106 120 mg SD

Urine sample was collected from participants at indicated time point for analysis of pH.

Part 1 Cohort A: pH Value by Visit- CCI15106 30 mg BID

Urine samples were collected from participants at indicated time points for analysis of pH.

Part 1 Cohort B: pH Value by Visit- CCI15106 60 mg BID

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 1: pH Value by Visit- Placebo

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 1 Cohort C: pH Value by Visit- CCI15106 in Bystanders

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 2 Cohort A: pH Value by Visit- CCI15106

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 2 Cohort B: pH Value by Visit- CCI15106 60 mg BID

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 60 mg SD

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 120 mg SD

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine sample was collected from participants at indicated time point for analysis of specific gravity.

Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 30 mg BID

Part 1 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of Specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 1: Specific Gravity Value by Visit- Placebo

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of Specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Part 1 Cohort C: Specific Gravity Value by Visit- CCI15106 in Bystanders

Part 2 Cohort A: Specific Gravity Value by Visit- CCI15106

Part 2 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID

Part 1: Number of Participants With Worst Case Post-Baseline 12-lead Electrocardiogram (ECG) of PCI in CCI15106

PCI ranges for the ECG parameters were as follows: absolute QTc interval >450 and <480, >=480 and <500, >=500 milliseconds (msec), absolute PR interval <110 and >220 msec and absolute QRS interval <75 and >110 msec. QTcF=Frederica's QT interval corrected for heart rate; QTcB=Bazett's QT interval corrected for heart rate. Data for worst case post-Baseline has been reported.

Part 1: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI in Bystander

PCI ranges for the ECG parameters were as follows: absolute QTc interval >450 and <480, >=480 and <500, >=500 msec, absolute PR interval <110 and >220 msec and absolute QRS interval <75 and >110 msec. Data for worst case post-Baseline has been reported.

Part 2: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI

Part 1: Number of Participants With Abnormal Telemetry Findings

Continuous cardiac telemetry was performed from approximately 0.5 hour (pre-dose) to 4 hours post-dose. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Part 2: Number of Participants With Abnormal Telemetry Findings

Continuous cardiac telemetry was performed from approximately 0.5 hour (pre-dose) to 4 hours post-dose. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Part 1: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Indicated Time Points

FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using standard spirometry. Percent predicted FEV1 was calculated as: Percent predicted FEV1=(maximum FEV1 divided by predicted normal FEV1)*100.

Part 1: Percent Predicted Forced Vital Capacity (FVC) at Indicated Time Points

FVC is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC was measured using standard spirometry. Percent predicted FVC was calculated as: Percent predicted FVC=(maximum FVC divided by predicted normal FVC)*100.

Part 2: Percent Predicted FEV1 at Indicated Time Points

Part 2: Percent Predicted FVC at Indicated Time Points

Part 1: Number of Participants With Vital Signs Values of PCI

PCI ranges for the vital signs parameters were as follows: systolic blood pressure (SBP) <85 and >160 millimeters of mercury (mmHg), diastolic blood pressure (DBP) <45 and >100 mmHg and heart rate <40 and >110 beats per minute (bpm). Data for the participants with high and low values has been reported.

Part 1: Number of Participants With Vital Signs Values of PCI in Bystanders

PCI ranges for the vital signs parameters were as follows: SBP <85 and >160 mmHg, DBP <45 and >100 mmHg and heart rate <40 and >110 bpm. Data for the participants with high and low values has been reported.

Part 2: Number of Participants With Vital Signs Values of PCI

Part 1 Cohort A: Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the pharmacokinetics (PKs) of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-t) data. PK population consisted of participants who received at least one dose of study treatment and who undergo plasma PK sampling and had at least one post-dose concentration result.

Part 1 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 120 mg on Day 3

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of AUC(0-t) data.

Part 2 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-t) data.

Part 1 Cohort A: Maximum Observed Plasma Concentration (Cmax) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of Cmax data.

Part 1 Cohort A: Cmax After Single Dose Administration of CCI15106 120 mg on Day 3

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of Cmax data.

Part 2 Cohort A: Cmax After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of Cmax data.

Part 1 Cohort A: Time of Maximum Concentration (Tmax) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of tmax data.

Part 1 Cohort A: Tmax After Single Dose Administration of CCI15106 120 mg on Day 3

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of tmax data.

Part 2 Cohort A: Tmax After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of tmax data.

Part 1 Cohort A: AUC From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-infinity) data.

Part 1 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 120 mg on Day 3

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of AUC(0-infinity) data.

Part 2 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-infinity) data.

Part 1 Cohort A: Elimination Half-life (t1/2) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of t1/2 data.

Part 1 Cohort A: t1/2 After Single Dose Administration of CCI15106 120 mg on Day 3

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of t1/2 data.

Part 2 Cohort A: t1/2 After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of t1/2 data.

Part 1 Cohort A: Clearance (CL/F) After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of CL/F data.

Part 1 Cohort A: CL/F After Single Dose Administration of CCI15106 120 mg on Day 3

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of CL/F data.

Part 2 Cohort A: CL/F After Single Dose Administration of CCI15106 60 mg on Day 1

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of CL/F data.

Part 1 Cohort A: AUC From Time Zero to End of Dosing Interval (AUC[0-tau]) After Repeated Dose Administration of CCI15106 30 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of AUC(0-tau) data.

Part 1 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of AUC(0-tau) data.

Part 2 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of AUC(0-tau) data.

Part 1 Cohort A: Cmax After Repeated Dose Administration of CCI15106 30 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of Cmax data.

Part 1 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of Cmax data.

Part 2 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of Cmax data.

Part 1 Cohort A: Tmax After Repeated Dose Administration of CCI15106 30 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of tmax data.

Part 1 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of tmax data.

Part 2 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of tmax data.

Part 1 Cohort A: t1/2 After Repeated Dose Administration of CCI15106 30 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of t1/2 data.

Part 1 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of t1/2 data.

Part 2 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of t1/2 data.

Part 1: Concentration of CCI15106 in Plasma of Bystanders: Cohort C

Blood samples were collected from bystanders 15 minutes after dosing at indicated time points. Bystander PK population consisted of participants who were present at least once in the room with the participant receiving the dose, undergo plasma PK sampling and had post-dose concentration result.

Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Bystander: Cohort C

Personal exposure air samples were collected on filters placed on each bystander after the first daily dose at indicated time points. The filters were used to measure CCI15106 concentration in the person's breathing zone. Fixed location concentrations were measured near window, near door, back to wall and facing wall in the dosing room over 15 minutes post-dose. Each bystander had a filter attached to their study clothing. The filters were measured for CCI15106. This was a single measurement from the filter for each bystsander. The locations (near window, near door, back to wall and facing wall) were just to record where the bystander was located in the room.

Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Stationary Pumps: Cohort C

Static air samples were collected on filters within air pumps positioned in two locations (bench and corner) in the room. Sampling devices attached to sampling pumps were used to measure CCI15106 concentration. Fixed location concentrations were measured in corner of room and on bench at back of room over 20 minutes and 60 minutes post-dosing.

Secondary Outcome Measures

Part 1: Concentration of CCI15106 in Lung Epithelial Lining Fluid (ELF) in Repeated Dose of Cohort B 60 mg

Bronchoalveolar lavage samples for ELF concentration analysis of CCI15106 were collected up to Day 13. Participants who received at least one dose of study treatment and who underwent bronchoalveolar lavage (BAL) sampling and had post-dose lung ELF CCI15106 and urea concentration result were included in BAL PK Population.

Part 2: Concentration of CCI15106 in ELF in Repeated Dose of Cohort B 60 mg

BAL samples for ELF concentration analysis of CCI15106 were collected up to Day 13.

Part 1: Number of Participants With Medical Device Incidents in CCI15106

A medical device incident is any malfunction or deterioration in the characteristics and/or performance of a device as well as any inadequacy in the labeling or the instructions for use which, directly or indirectly, might lead to or might have led to the death of a participant/user/other person or to a serious deterioration in his/her state of health.

Full Information

NCT ID

NCT03235726

First Posted

July 11, 2017

Last Updated

June 26, 2020

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT03235726

Brief Title

Study of Safety and Drug Levels of CCI15106 Inhalation Powder in Healthy Adults and Adults With Moderate Chronic Obstructive Pulmonary Disease. Study of CCI15106 Levels in People Standing Near the Person Inhaling the Drug

Official Title

A Double-blind (Sponsor Unblind), Randomized, Placebo-controlled, Single and Repeat Escalating Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of CCI15106 Inhalation Powder in Healthy Participants and Participants With Moderate Chronic Obstructive Pulmonary Disease (COPD) Including Evaluation of Environmental and Healthy By-stander Exposure Levels During Dosing

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

July 13, 2017 (Actual)

Primary Completion Date

June 19, 2018 (Actual)

Study Completion Date

June 19, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This single and repeat increasing dose study will collect information on safety, tolerability and drug levels in the body of the CCI15106 inhalation powder. The study will also look at the level of CCI15106 that will be released into the air and may be found in the blood of the people standing around the person inhaling it (bystanders). This is a two-part study in which Part 1 will enroll healthy subjects and look at environmental and bystander exposure and Part 2 will enroll subjects with moderate COPD. Approximately 36 healthy subjects and approximately 22 subjects with COPD will be randomized in this study for dosing. The total study duration will be 82 days for Cohort A Part 1; 75 days for Cohort B Part 1 and Cohort C Part 1; 77 days for Cohort A Part 2; and 90 days for Cohort B Part 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Disease, Chronic Obstructive

Keywords

bystander, inhalation powder, monodose device, COPD, pharmacokinetics, safety, Healthy, CCI15106, tolerability

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

In this study, subjects will be randomized to receive either study drug or placebo in a parallel manner.

Masking

ParticipantInvestigator

Masking Description

This is a double blind, randomized study and subject and investigator will be blinded.

Allocation

Randomized

Enrollment

52 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort A, Part 1: Active

Arm Type

Experimental

Arm Description

Arm Title

Cohort A, Part 1: Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Cohort B, Part 1: Active

Arm Type

Experimental

Arm Description

60 mg of CCI15106 BID will be administered by inhalation route for 14 days to healthy subjects.

Arm Title

Cohort B, Part 1: Placebo

Arm Type

Placebo Comparator

Arm Description

60 mg of placebo BID will be administered by inhalation route for 14 days to healthy subjects.

Arm Title

Cohort C, Part 1: bystanders

Arm Type

No Intervention

Arm Description

Healthy subjects will be enrolled to follow bystander exposure and will be studied concomitantly with Cohort B.

Arm Title

Cohort A, Part 2: Active

Arm Type

Experimental

Arm Description

60 mg single dose of CCI15106 will be administered by inhalation route to subjects with COPD.

Arm Title

Cohort A, Part 2: Placebo

Arm Type

Placebo Comparator

Arm Description

60 mg single dose of placebo will be administered by inhalation route to subjects with COPD.

Arm Title

Cohort B, Part 2: Active

Arm Type

Experimental

Arm Description

60 mg BID dose of CCI15106 will be administered by inhalation route for 14 days to subjects with COPD.

Arm Title

Cohort B, Part 2: Placebo

Arm Type

Placebo Comparator

Arm Description

60 mg BID dose of placebo will be administered by inhalation route for 14 days to subjects with COPD.

Intervention Type

Drug

Intervention Name(s)

CCI15106

Intervention Description

One capsule (single dose or repeat dose) of 30 mg of CCI15106 will be administered to healthy subjects and subjects with COPD via inhalation route using Monodose RS01 device. The morning dose will be taken in fasting state and for repeat dose; the evening dose will be taken at least 2 hours after food.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

One capsule of placebo will be administered to healthy subjects and subjects with COPD via inhalation route using Monodose RS01 device. The morning dose will be taken in fasting state and for repeat dose; the evening dose will be taken at least 2 hours after food.

Primary Outcome Measure Information:

Title

Part 1 Cohort A: Number of Participants With Non-serious Adverse Events (NSAEs) and Serious Adverse Events (SAEs) in CCI15106

Description

Time Frame

Up to 51 days

Title

Part 1 Cohort B: Number of Participants With NSAEs and SAEs in CCI15106

Description

Time Frame

Up to 46 days

Title

Part 1 Cohort C: Number of Participants With NSAEs and SAEs in Bystanders

Description

Time Frame

Up to 46 days

Title

Part 2 Cohort A: Number of Participants With NSAEs and SAEs

Description

Time Frame

Up to 33 days

Title

Part 2 Cohort B: Number of Participants With NSAEs and SAEs

Description

Time Frame

Up to 46 days

Title

Part 1: Number of Participants With Hematology Values of Potential Clinical Importance (PCI) in CCI15106

Description

Time Frame

Up to 51 days

Title

Part 1: Number of Participants With Hematology Values of PCI in Bystanders

Description

Time Frame

Up to 46 days

Title

Part 2: Number of Participants With Hematology Values of PCI

Description

Time Frame

Up to 46 days

Title

Part 1: Number of Participants With Clinical Chemistry Values of PCI in CCI15106

Description

Time Frame

Up to 51 days

Title

Part 1: Number of Participants With Clinical Chemistry Values of PCI in Bystanders

Description

Time Frame

Up to 46 days

Title

Part 2: Number of Participants With Clinical Chemistry Values of PCI

Description

Time Frame

Up to 46 days

Title

Part 1 Cohort A: Potential of Hydrogen (pH) Value by Visit- CCI15106 60 mg SD

Description

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1) and Day 2

Title

Part 1 Cohort A: pH Value by Visit- CCI15106 120 mg SD

Description

Urine sample was collected from participants at indicated time point for analysis of pH.

Time Frame

Day 5

Title

Part 1 Cohort A: pH Value by Visit- CCI15106 30 mg BID

Description

Urine samples were collected from participants at indicated time points for analysis of pH.

Time Frame

Days 12 and 22

Title

Part 1 Cohort B: pH Value by Visit- CCI15106 60 mg BID

Description

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1), Days 7 and 15

Title

Part 1: pH Value by Visit- Placebo

Description

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1), Days 2, 5, 7, 12, 15 and 22

Title

Part 1 Cohort C: pH Value by Visit- CCI15106 in Bystanders

Description

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1), Days 7 and 15

Title

Part 2 Cohort A: pH Value by Visit- CCI15106

Description

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1) and Day 2

Title

Part 2 Cohort B: pH Value by Visit- CCI15106 60 mg BID

Description

Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1), Days 7 and 15

Title

Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 60 mg SD

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 120 mg SD

Description

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine sample was collected from participants at indicated time point for analysis of specific gravity.

Time Frame

Day 5

Title

Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 30 mg BID

Description

Time Frame

Days 12 and 22

Title

Part 1 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID

Description

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of Specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1), Days 7 and 15

Title

Part 1: Specific Gravity Value by Visit- Placebo

Description

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of Specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

Time Frame

Baseline (Day -1), Days 2, 5, 7, 12, 15 and 22

Title

Part 1 Cohort C: Specific Gravity Value by Visit- CCI15106 in Bystanders

Description

Time Frame

Baseline (Day -1), Days 7 and 15

Title

Part 2 Cohort A: Specific Gravity Value by Visit- CCI15106

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Part 2 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID

Description

Time Frame

Baseline (Day -1), Days 7 and 15

Title

Part 1: Number of Participants With Worst Case Post-Baseline 12-lead Electrocardiogram (ECG) of PCI in CCI15106

Description

Time Frame

Up to 51 days

Title

Part 1: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI in Bystander

Description

Time Frame

Up to 46 days

Title

Part 2: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI

Description

Time Frame

Up to 46 days

Title

Part 1: Number of Participants With Abnormal Telemetry Findings

Description

Time Frame

Days 1, 3, 6, 7, 12 and 18: 0.5 hour (pre-dose) to 4 hours post-dose

Title

Part 2: Number of Participants With Abnormal Telemetry Findings

Description

Time Frame

Days 1, 7, 12 and 13: 0.5 hour (pre-dose) to 4 hours post-dose

Title

Part 1: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Indicated Time Points

Description

Time Frame

Days 1, 3, 6 and 19: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 8, 11 and 16: pre-dose and 4 hours post-dose; Day 14: pre-dose, 0.5, 1 and 4 hours post-dose

Title

Part 1: Percent Predicted Forced Vital Capacity (FVC) at Indicated Time Points

Description

Time Frame

Days 1, 3, 6 and 19: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 8, 11 and 16: pre-dose and 4 hours post-dose; Day 14: pre-dose, 0.5, 1 and 4 hours post-dose

Title

Part 2: Percent Predicted FEV1 at Indicated Time Points

Description

Time Frame

Day 1 and 14: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 3, 6 and 11: pre-dose and 4 hours post-dose

Title

Part 2: Percent Predicted FVC at Indicated Time Points

Description

Time Frame

Day 1 and 14: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 3, 6 and 11: pre-dose and 4 hours post-dose

Title

Part 1: Number of Participants With Vital Signs Values of PCI

Description

Time Frame

Up to 51 days

Title

Part 1: Number of Participants With Vital Signs Values of PCI in Bystanders

Description

Time Frame

Up to 46 days

Title

Part 2: Number of Participants With Vital Signs Values of PCI

Description

Time Frame

Up to 46 days

Title

Part 1 Cohort A: Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

Title

Part 1 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 120 mg on Day 3

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of AUC(0-t) data.

Time Frame

Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 2 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-t) data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: Maximum Observed Plasma Concentration (Cmax) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of Cmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

Title

Part 1 Cohort A: Cmax After Single Dose Administration of CCI15106 120 mg on Day 3

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of Cmax data.

Time Frame

Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 2 Cohort A: Cmax After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of Cmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: Time of Maximum Concentration (Tmax) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of tmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

Title

Part 1 Cohort A: Tmax After Single Dose Administration of CCI15106 120 mg on Day 3

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of tmax data.

Time Frame

Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 2 Cohort A: Tmax After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of tmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: AUC From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-infinity) data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

Title

Part 1 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 120 mg on Day 3

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of AUC(0-infinity) data.

Time Frame

Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 2 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-infinity) data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: Elimination Half-life (t1/2) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of t1/2 data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

Title

Part 1 Cohort A: t1/2 After Single Dose Administration of CCI15106 120 mg on Day 3

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of t1/2 data.

Time Frame

Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 2 Cohort A: t1/2 After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of t1/2 data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: Clearance (CL/F) After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of CL/F data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

Title

Part 1 Cohort A: CL/F After Single Dose Administration of CCI15106 120 mg on Day 3

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of CL/F data.

Time Frame

Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 2 Cohort A: CL/F After Single Dose Administration of CCI15106 60 mg on Day 1

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of CL/F data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: AUC From Time Zero to End of Dosing Interval (AUC[0-tau]) After Repeated Dose Administration of CCI15106 30 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of AUC(0-tau) data.

Time Frame

Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 1 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of AUC(0-tau) data.

Time Frame

Days 1 and 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose

Title

Part 2 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of AUC(0-tau) data.

Time Frame

Days 1 and 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose

Title

Part 1 Cohort A: Cmax After Repeated Dose Administration of CCI15106 30 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of Cmax data.

Time Frame

Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 1 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of Cmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 2 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of Cmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: Tmax After Repeated Dose Administration of CCI15106 30 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of tmax data.

Time Frame

Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 1 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of tmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 2 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of tmax data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1 Cohort A: t1/2 After Repeated Dose Administration of CCI15106 30 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of t1/2 data.

Time Frame

Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

Title

Part 1 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of t1/2 data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 2 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg

Description

Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of t1/2 data.

Time Frame

Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

Title

Part 1: Concentration of CCI15106 in Plasma of Bystanders: Cohort C

Description

Time Frame

Days 1, 7 and 14: pre-dose, 15 minutes post-dose

Title

Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Bystander: Cohort C

Description

Time Frame

Days 1, 7 and 14: 15 minutes post-dose

Title

Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Stationary Pumps: Cohort C

Description

Time Frame

Days 1, 7 and 14: 20 and 60 minutes post-dose

Secondary Outcome Measure Information:

Title

Part 1: Concentration of CCI15106 in Lung Epithelial Lining Fluid (ELF) in Repeated Dose of Cohort B 60 mg

Description

Time Frame

Up to Day 13

Title

Part 2: Concentration of CCI15106 in ELF in Repeated Dose of Cohort B 60 mg

Description

BAL samples for ELF concentration analysis of CCI15106 were collected up to Day 13.

Time Frame

Up to Day 13

Title

Part 1: Number of Participants With Medical Device Incidents in CCI15106

Description

Time Frame

Up to Day 19

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Some important Inclusion Criteria: For healthy subjects and bystanders: 18 to 65 years of age. Healthy as determined by a doctor. Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period. Women who are not pregnant or breastfeeding, and not of childbearing potential. For subjects with COPD: 40 to 75 years of age. Diagnosed with moderate COPD by a doctor. Have breathing test results that are consistent with moderate COPD as defined in the study protocol. A smoker or an ex-smoker. Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period. Women who are not pregnant or breastfeeding, and not of childbearing potential. Some Important Exclusion Criteria: For healthy subjects and bystanders: History of liver disease. Use of over-the-counter or prescription drugs (including vitamins) 7 days before the study until completion of the follow-up visit. Participation in the study would result in loss of more than 500 milliliter (mL) of blood within 3 months. Participation in another clinical trial with an investigational product within about 3 months before this study. Positive drug/alcohol screen. Regular use of known drugs of abuse. Regular alcohol consumption within 3 months before the study. Breath test indicative of smoking at study start. Documented lactose allergy/intolerance. Men whose partner is pregnant or breastfeeding cannot participate. Certain blood test results may not allow subjects to participate, as described in the study protocol. For subjects with COPD: History of liver disease. Poorly controlled COPD disease as, for example, more than 2 exacerbations of COPD per year. Some respiratory conditions, like for example active tuberculosis, lung cancer or any other respiratory condition. Subjects with other respiratory conditions (for example, clinically significant: asthma, pulmonary fibrosis, bronchiectasis) are excluded if these conditions are the primary cause of their respiratory symptoms. Unstable or uncontrolled cardiac disease. Problems with kidney function as defined in the study protocol. Past or current medical conditions or diseases that are not well controlled. Subjects are not allowed to take oral corticosteroids from 4 weeks prior to screening and for the duration of the study. Subjects taking medications for any chronic conditions have to be on stable doses for 4 weeks before screening and until after study treatment is finished. Use of short-acting inhaled bronchodilators is allowed, but subjects must be able to stop their medications several times during the study. Use of long-acting bronchodilators is allowed, but subjects must be able to change the schedule of their medications twice during the study. Participation in the study would result in loss of more than 500 mL within 3 months. Participation in another clinical trial with an investigational product within about 3 months before this study. Positive drug/alcohol screen. Regular use of known drugs of abuse. Regular alcohol consumption within 3 months before the study. Unable to refrain from smoking for certain periods during the study (maximum about 6 hours). Documented lactose allergy/intolerance. Men whose partner is pregnant or breastfeeding cannot participate. Certain blood test results may not allow subjects to participate, as described in the study protocol.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Park Royal

State/Province

London

ZIP/Postal Code

NE10 7EW

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (click on the link provided below)

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

https://clinicalstudydatarequest.com/Posting.aspx?ID=20373

Citations:

PubMed Identifier

32071044

Citation

Dumont EF, Oliver AJ, Ioannou C, Billiard J, Dennison J, van den Berg F, Yang S, Chandrasekaran V, Young GC, Lahiry A, Starbuck DC, Harrell AW, Georgiou A, Hopchet N, Gillies A, Baker SJ. A Novel Inhaled Dry-Powder Formulation of Ribavirin Allows for Efficient Lung Delivery in Healthy Participants and Those with Chronic Obstructive Pulmonary Disease in a Phase 1 Study. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02267-19. doi: 10.1128/AAC.02267-19. Print 2020 Apr 21.

Results Reference

derived

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