A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06882961 in Japanese Adults With Type 2 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT04552470
• Recruitment Status: Completed
• First Posted: September 17, 2020
• Results First Posted: March 11, 2022
• Last Update Posted: March 11, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 11, 2020
• First Posted Date: September 17, 2020
• Results First Submitted Date: December 14, 2021
• Results First Posted Date: March 11, 2022
• Last Update Posted Date: March 11, 2022
• Actual Study Start Date: October 26, 2020
• Actual Primary Completion Date: March 25, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2022)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks) ]
  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 [ Time Frame: Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks) ]
  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 [ Time Frame: Baseline (1 Day before dosing) up to last dose (maximum up to Week 8) ]
  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 [ Time Frame: Baseline (1 Day before dosing) up to last dose (maximum up to Week 8) ]
  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.

Original Primary Outcome Measures (submitted: September 11, 2020)

• Number of Participants With Treatment Emergent Treatment-Related Adverse Events [ Time Frame: Baseline up to 35 days after last dose (Day 91) ]
• Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 14 days after last dose (Day 70) ]
• Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Baseline up to 14 days after last dose (Day 70) ]
• Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: Baseline up to 14 days after last dose (Day 70) ]

Current Secondary Outcome Measures (submitted: March 10, 2022)

• Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) 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 and 56 ]
  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 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 ]
• 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 ]
• Terminal Phase Half-Life (t1/2) of PF-06882961 [ Time Frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56 ]
  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.

Original Secondary Outcome Measures (submitted: September 11, 2020)

• Area under the Concentration-Time Curve [ Time Frame: 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours on Day 1; 0, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56; ]
• Maximum Observed Plasma Concentration [ Time Frame: 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours on Day 1; 0, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56; ]
• Time to Reach Maximum Observed Plasma Concentration [ Time Frame: 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours on Day 1; 0, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56; ]
• Plasma Terminal Half-Life [ Time Frame: 0, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56; ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Type 2 Diabetes Mellitus

Intervention

• Drug: Placebo
  3 matching placebo tablets taken twice a day (BID)
• Drug: PF-06882961
  Participants will be randomized to one of 3 active doses (40, 80, or 120 mg), taking 3 tablets twice daily for 8 weeks.

Study Arms

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: PF-06882961 40 mg
  Participants will be titrated up to 2 weeks to reach desired dose level
  Intervention: Drug: PF-06882961
• Experimental: PF-06882961 80 mg
  Participants will be titrated up to 4 weeks to reach desired dose level
  Intervention: Drug: PF-06882961
• Experimental: PF-06882961 120 mg
  Participants will be titrated up to 6 weeks to reach desired dose level
  Intervention: Drug: PF-06882961

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 2, 2021): 37
• Original Estimated Enrollment (submitted: September 11, 2020): 36
• Actual Study Completion Date: March 25, 2021
• Actual Primary Completion Date: March 25, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04552470
• Other Study ID Numbers: C3421015
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No
• 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.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2022