Repeat Dose Study in Male Healthy Volunteer Smokers
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
SB-656933
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring Smoker,, Male,, Chronic Obstructive Lung Disease, Cystic Fibrosis,, Healthy Volunteer,
Eligibility Criteria
Inclusion Criteria:
- Healthy adult male smokers who are between 18-65 years of age with normal genitourinary anatomy based on physical examination.
- The subjects should have a normal colour Doppler epididymal ultrasound (normal blood flow and epididymal morphology) at screening.
- The first 10 mL of urine voided (VB1) should be normal at screening and pre-dose.
- Male subjects must agree to abstain from or use a condom during sexual intercourse with pregnant females; or use a condom/spermicide, in addition to having their female partner use another form of contraception, such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation, if engaging in sexual intercourse with a female partner who could become pregnant. This criterion must be followed from the time of the first dose of study medication until 84 days after the last dose of study medication.
- The subject has a QTc(B) <450msec at screening or prior to dosing
- Body weight = 50 kg (110 pounds) and body mass index (BMI) between 19 and 30 inclusive where: BMI =weight in kg/(height in meters)2
- Healthy male smokers must smoke more than 10 cigarettes per day, for at least 2 months prior to screening and less than 30 cigarettes per day at the time of enrolment.
- Subjects with Forced Expiratory Volume (FEV1)=80% predicted and FEV1/Forced Vital Capacity (FVC) ratio=0.7.
- Signed and dated written informed consent prior to admission to the study
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Exclusion Criteria:
- Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or 12-lead ECG.
- The subject has liver function tests (LFT) elevated above the reference range at pre-study screening that remain elevated with a repeat LFT (to be discussed with the sponsor, if necessary).
- Subjects with absolute neutrophil count (ANC) = 2.0x109/L.
- Subjects who have previously been exposed to testicular radiotherapy.
- Subjects who have had previous testicular or prostate surgery including vasectomy.
- History of prostatitis, epididymitis, epididymal cysts, structural abnormalities or testicular cancer.
- Subjects with abnormalities of the renal tract, renal stones or history of Urinary Tract Infections (UTI's).
- Positive drug or alcohol test at screening or prior to dosing.
- Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody at screening
- Use of prescription or non-prescription medication in the last 7 days or 5 half-lives (whichever is longer) , particularly drugs that are P450 CYP3A4, CYP2B6, CYP2C8 or OATP1B1 substrates with a narrow therapeutic index , and including vitamins and herbal remedies such as St John's Wort prior to dose of study medication.
- Consumption of grapefruit or grapefruit juice within seven days prior to the first dose of study medication.
- Donation of blood in excess of 500 mL within a 56 day period prior to dosing.
- Exposure to more than 3 new chemical entities within 12 months prior to the first dosing day.
- Participation in a trial with any drug within 3 months before the start of the study or participation in a trial with a new chemical entity within 4 months before the start of the study.
- Are receiving treatment for smoking cessation.
- Are using tobacco products other than cigarettes (e.g. pipes, cigars, snuff, chewing tobacco).
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Subjects receiving SB-656933
Subjects receiving placebo
Arm Description
Eligible subjects will be randomized to receive once daily doses of 100 milligrams of SB- 656933 for 14 days.
Eligible subjects will be randomized to receive placebo for 14 days.
Outcomes
Primary Outcome Measures
-what the body does to the drug over a 17 day of dosing with 100mg of SB656933. -Safety of SB-656933: Adverse events, blood pressure, heart rate, electrocardiogram, epididymal ultrasound and lab tests
-what the body does to the drug over a 17 day of dosing with 100mg of SB656933 by taking PK samples at:
-Safety of SB-656933: Adverse events every day for entire study period: blood pressure , heart rate and temperature
electrocardiogram
Secondary Outcome Measures
- Looking at the actual sample size data to determine a larger theoretical population. -What the drug does to the body when present at its lowest level on day 14 as compared before drug given.
Safety and tolerability of SB-656933 in subjects with cystic fibrosis, including adverse events, vital signs, clinical laboratory assessments, electrocardiographic (ECG) parameters, and lung function (FVC, FEV1)
Fluorocytometric quantitation of CXCL1-induced CD11b expression on peripheral blood neutrophils in ex-vivo assay.
Neutrophil shape change in response to stimulation with CXCL-1 in whole blood ex-vivo gated autofluorescence forward scatter (GAFS) assay.
Looking at the actual sample size data to determine a larger theoretical population.
What the drug does to the body when present at its lowest level on day 14 as compared before drug given.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00615576
Brief Title
Repeat Dose Study in Male Healthy Volunteer Smokers
Official Title
A Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SB-656933 Following 14 Days Repeat Dosing in Healthy Male Smokers
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
March 26, 2008 (Actual)
Primary Completion Date
July 24, 2008 (Actual)
Study Completion Date
July 24, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a 4 to 6 week study to look at the safety and PK profile of SB656933 in healthy male smokers
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
Smoker,, Male,, Chronic Obstructive Lung Disease, Cystic Fibrosis,, Healthy Volunteer,
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Subjects receiving SB-656933
Arm Type
Experimental
Arm Description
Eligible subjects will be randomized to receive once daily doses of 100 milligrams of SB- 656933 for 14 days.
Arm Title
Subjects receiving placebo
Arm Type
Placebo Comparator
Arm Description
Eligible subjects will be randomized to receive placebo for 14 days.
Intervention Type
Drug
Intervention Name(s)
SB-656933
Intervention Description
SB-656933 will be available as white film coated, round tablet and will be available in strengths of 50 milligrams, administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
A placebo tablet to visually match the SB-656933 tablet will also be supplied, administered orally once daily.
Primary Outcome Measure Information:
Title
-what the body does to the drug over a 17 day of dosing with 100mg of SB656933. -Safety of SB-656933: Adverse events, blood pressure, heart rate, electrocardiogram, epididymal ultrasound and lab tests
Time Frame
17 days
Title
-what the body does to the drug over a 17 day of dosing with 100mg of SB656933 by taking PK samples at:
Time Frame
pre-dose and at 0.5,1,2,3,4,6,8,12 and 24 hours post-dose on days 1 and 14; pre-dose on Day7. Additional samples at 32, 48 and 72 hours post-dose wil
Title
-Safety of SB-656933: Adverse events every day for entire study period: blood pressure , heart rate and temperature
Time Frame
taken pre-dose, 30min, 1hr, and 2hr on Day1, Day2, Day7 and Day14 (supine only);
Title
electrocardiogram
Time Frame
pre-dose, 2hr and 4 hr on Day1
Secondary Outcome Measure Information:
Title
- Looking at the actual sample size data to determine a larger theoretical population. -What the drug does to the body when present at its lowest level on day 14 as compared before drug given.
Time Frame
17 days
Title
Safety and tolerability of SB-656933 in subjects with cystic fibrosis, including adverse events, vital signs, clinical laboratory assessments, electrocardiographic (ECG) parameters, and lung function (FVC, FEV1)
Time Frame
Up to Day 28
Title
Fluorocytometric quantitation of CXCL1-induced CD11b expression on peripheral blood neutrophils in ex-vivo assay.
Time Frame
Up to Day 14
Title
Neutrophil shape change in response to stimulation with CXCL-1 in whole blood ex-vivo gated autofluorescence forward scatter (GAFS) assay.
Time Frame
Up to Day 14
Title
Looking at the actual sample size data to determine a larger theoretical population.
Time Frame
Up to Day 14
Title
What the drug does to the body when present at its lowest level on day 14 as compared before drug given.
Time Frame
on day 14
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy adult male smokers who are between 18-65 years of age with normal genitourinary anatomy based on physical examination.
The subjects should have a normal colour Doppler epididymal ultrasound (normal blood flow and epididymal morphology) at screening.
The first 10 mL of urine voided (VB1) should be normal at screening and pre-dose.
Male subjects must agree to abstain from or use a condom during sexual intercourse with pregnant females; or use a condom/spermicide, in addition to having their female partner use another form of contraception, such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation, if engaging in sexual intercourse with a female partner who could become pregnant. This criterion must be followed from the time of the first dose of study medication until 84 days after the last dose of study medication.
The subject has a QTc(B) <450msec at screening or prior to dosing
Body weight = 50 kg (110 pounds) and body mass index (BMI) between 19 and 30 inclusive where: BMI =weight in kg/(height in meters)2
Healthy male smokers must smoke more than 10 cigarettes per day, for at least 2 months prior to screening and less than 30 cigarettes per day at the time of enrolment.
Subjects with Forced Expiratory Volume (FEV1)=80% predicted and FEV1/Forced Vital Capacity (FVC) ratio=0.7.
Signed and dated written informed consent prior to admission to the study
The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Exclusion Criteria:
Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or 12-lead ECG.
The subject has liver function tests (LFT) elevated above the reference range at pre-study screening that remain elevated with a repeat LFT (to be discussed with the sponsor, if necessary).
Subjects with absolute neutrophil count (ANC) = 2.0x109/L.
Subjects who have previously been exposed to testicular radiotherapy.
Subjects who have had previous testicular or prostate surgery including vasectomy.
History of prostatitis, epididymitis, epididymal cysts, structural abnormalities or testicular cancer.
Subjects with abnormalities of the renal tract, renal stones or history of Urinary Tract Infections (UTI's).
Positive drug or alcohol test at screening or prior to dosing.
Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody at screening
Use of prescription or non-prescription medication in the last 7 days or 5 half-lives (whichever is longer) , particularly drugs that are P450 CYP3A4, CYP2B6, CYP2C8 or OATP1B1 substrates with a narrow therapeutic index , and including vitamins and herbal remedies such as St John's Wort prior to dose of study medication.
Consumption of grapefruit or grapefruit juice within seven days prior to the first dose of study medication.
Donation of blood in excess of 500 mL within a 56 day period prior to dosing.
Exposure to more than 3 new chemical entities within 12 months prior to the first dosing day.
Participation in a trial with any drug within 3 months before the start of the study or participation in a trial with a new chemical entity within 4 months before the start of the study.
Are receiving treatment for smoking cessation.
Are using tobacco products other than cigarettes (e.g. pipes, cigars, snuff, chewing tobacco).
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
London
ZIP/Postal Code
NW10 7NS
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Repeat Dose Study in Male Healthy Volunteer Smokers
We'll reach out to this number within 24 hrs