Multiple Escalating Oral Doses Study of PF-07081532 in Adult Participants With Type 2 Diabetes Mellitus

A Phase 1, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Escalating Oral Doses of PF-07081532 in Adult Participants With Type 2 Diabetes Mellitus

This is a randomized, placebo-controlled, double-blind (investigator- and participant-blinded), sponsor-open, dose-escalating study of PF-07081532 in patients with Type 2 diabetes on metformin (Parts A and C). The study may also enroll non-diabetic participants with obesity (Part B). Study participants will receive an investigational product or placebo every day for up to 28 days (Part A) or up to 42 days (Part B, optional; Part C, optional).

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple oral doses of PF-07081532 in participants with inadequately controlled T2DM on metformin and optionally in non-diabetic obese participants.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Other: Placebo; Drug: Clopidogrel; Drug: PF-07081532

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
  • Florida
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria for participants enrolling with T2DM:

• Type 2 Diabetes treated with a stable dose of metformin at least 500 mg per day for at least 2 months prior to screening visit and use of no other medications for glycemic control.
• HbA1c value between 7.0% and 10.5%, inclusive.

Key Exclusion Criterion for participants enrolling with T2DM:

-Type 1 Diabetes or secondary forms of diabetes.

Key Inclusion Criterion for participants enrolling with obesity:

-Obese (as indicated by screening BMI) non-diabetic adults.

Key Exclusion Criterion for participants enrolling with obesity:

--Type 1 or Type 2 Diabetes or secondary forms of diabetes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Obesity; Part B	Other: Placebo; Placebo once daily for up to 42 days.; Drug: Clopidogrel; Part B may include a drug-drug interaction study using open-label clopidogrel. Clopidrogrel may be given as two single doses of 75 mg administered on day -2 and day 41.; Other Names: Plavix
Placebo Comparator: Placebo Obesity; Part B	Other: Placebo; Placebo once daily for up to 42 days.; Drug: Clopidogrel; Part B may include a drug-drug interaction study using open-label clopidogrel. Clopidrogrel may be given as two single doses of 75 mg administered on day -2 and day 41.; Other Names: Plavix
Experimental: Active T2DM; Parts A and C	Drug: PF-07081532; Investigational Drug once daily for up to 42 days; multiple ascending dose design.
Placebo Comparator: Placebo T2DM; Parts A and C	Drug: PF-07081532; Investigational Drug once daily for up to 42 days; multiple ascending dose design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Treatment-Related Adverse Events	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	From the first dose up to 28-35 days after last administration of study intervention (that is a maximum of 63 days from first dose for Part A and a maximum of 77 days from first dose for Part B and Part C)
Number of Participants With Laboratory Abnormalities	Participants with laboratory abnormalities with ≥2 occurrences (without regard to baseline abnormality) that met pre-specified criteria were High-density lipoprotein (HDL) Cholesterol <0.8✕ lower limit of normal (LLN); Bicarbonate <0.9✕LLN; Calcitonin>1.0✕upper limit of normal (ULN); Triglycerides >1.3✕ULN; Aspartate Aminotransferase >3.0✕ULN; Low-density lipoprotein (LDL) Cholesterol >1.2✕ULN; Urine Glucose ≥1; Urine Ketones ≥1; Urine Leukocyte Esterase ≥1; Urine Leukocytes ≥20; Urine Hyaline Casts >1; Urine Hemoglobin ≥1; and Urine Nitrite ≥1.	From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)
Number of Participants With Vital Signs Abnormalities	Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in vital signs, were supine systolic blood pressure < 90 millimeters of mercury (mmHg), supine systolic blood pressure increase/decrease from baseline ≥ 30mmHg; supine diastolic blood pressure <50 mmHg, supine diastolic blood pressure increase/decrease from baseline ≥ 20mmHg; pulse rate <40 beats per minute (bpm) or >120 bpm.	From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)
Number of Participants With Abnormal Electrocardiogram (ECG)	The pre-specified categorical analysis criteria in ECG, were PR interval: value ≥ 300 milliseconds (msec), percentage change ≥ 25/50%; QRS duration: value ≥140 msec, percentage change ≥ 50%; QTcF interval: 450 < value ≤ 480 msec, 480 < value ≤ 500 msec, value >500 msec, and 30<change ≤ 60 msec, change >60 msec.	From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time 0 to 24 Hours (AUC24) Post Dose for PF-07081532	AUC24 is defined as area under the concentration-time profile from time 0 to 24 hours using Linear/Log trapezoidal method.	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C
Maximum Observed Plasma Concentration (Cmax) for PF-07081532	Cmax is defined as maximum plasma concentration observed directly from data.	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-07081532	Tmax is defined as time for Cmax observed directly from data as time of first occurrence.	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C
Time Measured for the Plasma Concentration to Decrease by One-Half (t1/2) for PF-07081532	t1/2 is defined as the time measured for the plasma concentration to decrease by one half.	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 28 for Part A, on Day 42 for Part B and Part C
Cumulative Amount of Drug Recovered Unchanged in Urine Over 24 Hours (Ae24) for PF-07081532	Ae24 is defined as cumulative amount of drug recovered unchanged in urine over 24 hours using the method of urine concentration * volume of urine.	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)
Percentage of Ae24 (Ae24%) for PF-07081532	Ae24% is defined as percent of dose recovered unchanged in urine over the 24 hours using the method of 100 * Ae24/Dose	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)
Renal Clearance (CLr) for PF-07081532	Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine over the dosing interval tau (Aetau) divided by area under the concentration time-curve from time 0 to time tau (AUCtau)	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2020
• Primary Completion (Actual): July 14, 2021
• Study Completion (Actual): July 14, 2021

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 9, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: C3991002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No