Back to resultsA Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06882961 in Japanese Adults With Type 2 Diabetes Mellitus
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Placebo
PF-06882961
Sponsored by
About this trial
This is an interventional basic science trial for Type 2 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Patients with T2DM who are treated with diet and exercise
- HbA1c greater than or equal to 7% and less than or equal to 10.5%
- Total body weight >50 kg (110 lb) with BMI 22.5 to 45.4 kg/m^2
Exclusion Criteria:
- Any condition possibly affecting drug absorption
- Diagnosis of Type 1 diabetes
- History of myocardial infarction, unstable angina, arterial revascularization, stroke, heart failure, or transient ischemic attack within 6 months of screening
- Any malignancy not considered cured
- Personal or family history of MTC or MEN2, or participants with suspected MTC
- Acute pancreatitis or history of chronic pancreatitis
- Symptomatic gallbladder disease
- Known medical history of active proliferative retinopathy and/or macular edema
- Known history of HIV, hepatitis B, hepatitis C or syphilis
- Supine blood pressure greater than or equal to 160 mmHg (systolic) or greater than or equal to 100 mmHg (diastolic)
- Clinically relevant ECG abnormalities
- Positive urine drug test
Sites / Locations
- P-one clinic, Keikokai medical corporation
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
PF-06882961 40 mg
PF-06882961 80 mg
PF-06882961 120 mg
Arm Description
Participants will be titrated up to 2 weeks to reach desired dose level
Participants will be titrated up to 4 weeks to reach desired dose level
Participants will be titrated up to 6 weeks to reach desired dose level
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. Treatment emergent AEs were events between first dose of study drug and approximately 4 weeks after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs.
Number of Participants With Clinical Laboratory Abnormalities
Leukocytes (10^9/liter [L]) bilirubin (micromol/L), glucose (millimoles [mmol]/L), triacylglycerol lipase (microkatals [microkat]/L): greater than (>) 1.5*upper limit normal (ULN); activated partial thromboplastin time (s): 1.1*ULN; HDL cholesterol (mmol/L), thyroid stimulating hormone (TSH) (milliunits [mU]/L): less than (<) 0.8*lower limit normal (LLN); LDL cholesterol (mmol/L), urate (mmol/L): >1.2*ULN; triglycerides: >1.3*ULN; aspartate aminotransferase (microkat/L), alanine aminotransferase (microkat/L), gamma glutamyl transferase (microkat/L): >3.0*ULN; cholesterol (mmol/L): >1.3*ULN; urine glucose, ketones urine protein, urine hemoglobin, urobilinogen, nitrite, leukocyte esterase: greater than or equal to (>=) 1; granular casts, hyaline casts: >1.
Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline
Supine systolic blood pressure (SBP) measured in millimeter of mercury (mmHg) had following categories: minimum of absolute SBP <90 mmHg, maximum of SBP >=30 mmHg decrease from baseline and maximum of SBP >=30 mmHg increase from baseline. Supine diastolic blood pressure (DBP) measured in mmHg had following categories: minimum of absolute DBP <50 mmHg, maximum of DBP >20 mmHg decrease from baseline and maximum of DBP >=20 mmHg increase from baseline. Supine pulse rate measured in beats per minute (BPM) had following categories: minimum of absolute supine pulse rate <40 BPM and maximum of absolute supine pulse rate >120 BPM. Baseline was defined as the time-matched value from the average of the triplicate recordings on Day -1.
Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline
PR interval had following categories: maximum absolute PR interval >=300 milliseconds (msec); when baseline PR interval >200 msec and maximum increase from baseline in PR interval >=25 percent; when baseline PR interval less than or equal to (<=) 200 msec and maximum increase from baseline in PR interval >=50 percent. QRS interval had following categories: maximum absolute QRS interval >=140 msec; maximum increase from baseline in QRS interval >=50 percent. QTC interval with Frederica's correction (QTCF) had following categories: absolute QTCF interval >450 msec to <=480 msec; absolute QTCF interval >480 msec to <=500 msec; absolute QTCF interval >500 msec; QTCF interval increase from baseline >=30 msec to <=60 msec; QTCF interval increase from baseline >60 msec.
Secondary Outcome Measures
Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961
AUC24= Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
Maximum Plasma Concentration (Cmax) Observed of PF-06882961
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961
Terminal Phase Half-Life (t1/2) of PF-06882961
t1/2 was calculated as loge (2) per kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04552470
Brief Title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06882961 in Japanese Adults With Type 2 Diabetes Mellitus
Official Title
AN 8-WEEK PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF TWICE DAILY PF-06882961 ADMINISTRATION IN JAPANESE ADULTS WITH TYPE 2 DIABETES MELLITUS
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
October 26, 2020 (Actual)
Primary Completion Date
March 25, 2021 (Actual)
Study Completion Date
March 25, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1, randomized, double blind (sponsor open), parallel, placebo controlled, twice daily oral dosing study of PF 06882961 in adult Japanese participants with T2DM inadequately controlled on diet and exercise alone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
PF-06882961 40 mg
Arm Type
Experimental
Arm Description
Participants will be titrated up to 2 weeks to reach desired dose level
Arm Title
PF-06882961 80 mg
Arm Type
Experimental
Arm Description
Participants will be titrated up to 4 weeks to reach desired dose level
Arm Title
PF-06882961 120 mg
Arm Type
Experimental
Arm Description
Participants will be titrated up to 6 weeks to reach desired dose level
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
3 matching placebo tablets taken twice a day (BID)
Intervention Type
Drug
Intervention Name(s)
PF-06882961
Intervention Description
Participants will be randomized to one of 3 active doses (40, 80, or 120 mg), taking 3 tablets twice daily for 8 weeks.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. Treatment emergent AEs were events between first dose of study drug and approximately 4 weeks after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs.
Time Frame
Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks)
Title
Number of Participants With Clinical Laboratory Abnormalities
Description
Leukocytes (10^9/liter [L]) bilirubin (micromol/L), glucose (millimoles [mmol]/L), triacylglycerol lipase (microkatals [microkat]/L): greater than (>) 1.5*upper limit normal (ULN); activated partial thromboplastin time (s): 1.1*ULN; HDL cholesterol (mmol/L), thyroid stimulating hormone (TSH) (milliunits [mU]/L): less than (<) 0.8*lower limit normal (LLN); LDL cholesterol (mmol/L), urate (mmol/L): >1.2*ULN; triglycerides: >1.3*ULN; aspartate aminotransferase (microkat/L), alanine aminotransferase (microkat/L), gamma glutamyl transferase (microkat/L): >3.0*ULN; cholesterol (mmol/L): >1.3*ULN; urine glucose, ketones urine protein, urine hemoglobin, urobilinogen, nitrite, leukocyte esterase: greater than or equal to (>=) 1; granular casts, hyaline casts: >1.
Time Frame
Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks)
Title
Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline
Description
Supine systolic blood pressure (SBP) measured in millimeter of mercury (mmHg) had following categories: minimum of absolute SBP <90 mmHg, maximum of SBP >=30 mmHg decrease from baseline and maximum of SBP >=30 mmHg increase from baseline. Supine diastolic blood pressure (DBP) measured in mmHg had following categories: minimum of absolute DBP <50 mmHg, maximum of DBP >20 mmHg decrease from baseline and maximum of DBP >=20 mmHg increase from baseline. Supine pulse rate measured in beats per minute (BPM) had following categories: minimum of absolute supine pulse rate <40 BPM and maximum of absolute supine pulse rate >120 BPM. Baseline was defined as the time-matched value from the average of the triplicate recordings on Day -1.
Time Frame
Baseline (1 Day before dosing) up to last dose (maximum up to Week 8)
Title
Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline
Description
PR interval had following categories: maximum absolute PR interval >=300 milliseconds (msec); when baseline PR interval >200 msec and maximum increase from baseline in PR interval >=25 percent; when baseline PR interval less than or equal to (<=) 200 msec and maximum increase from baseline in PR interval >=50 percent. QRS interval had following categories: maximum absolute QRS interval >=140 msec; maximum increase from baseline in QRS interval >=50 percent. QTC interval with Frederica's correction (QTCF) had following categories: absolute QTCF interval >450 msec to <=480 msec; absolute QTCF interval >480 msec to <=500 msec; absolute QTCF interval >500 msec; QTCF interval increase from baseline >=30 msec to <=60 msec; QTCF interval increase from baseline >60 msec.
Time Frame
Baseline (1 Day before dosing) up to last dose (maximum up to Week 8)
Secondary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961
Description
AUC24= Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
Time Frame
Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1 and 56
Title
Maximum Plasma Concentration (Cmax) Observed of PF-06882961
Time Frame
Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961
Time Frame
Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56
Title
Terminal Phase Half-Life (t1/2) of PF-06882961
Description
t1/2 was calculated as loge (2) per kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time Frame
Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with T2DM who are treated with diet and exercise
HbA1c greater than or equal to 7% and less than or equal to 10.5%
Total body weight >50 kg (110 lb) with BMI 22.5 to 45.4 kg/m^2
Exclusion Criteria:
Any condition possibly affecting drug absorption
Diagnosis of Type 1 diabetes
History of myocardial infarction, unstable angina, arterial revascularization, stroke, heart failure, or transient ischemic attack within 6 months of screening
Any malignancy not considered cured
Personal or family history of MTC or MEN2, or participants with suspected MTC
Acute pancreatitis or history of chronic pancreatitis
Symptomatic gallbladder disease
Known medical history of active proliferative retinopathy and/or macular edema
Known history of HIV, hepatitis B, hepatitis C or syphilis
Supine blood pressure greater than or equal to 160 mmHg (systolic) or greater than or equal to 100 mmHg (diastolic)
Clinically relevant ECG abnormalities
Positive urine drug test
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
P-one clinic, Keikokai medical corporation
City
Hachioji
State/Province
Tokyo
ZIP/Postal Code
192-0071
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C3421015
Description
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Learn more about this trial
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06882961 in Japanese Adults With Type 2 Diabetes Mellitus
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