Clinical trial NCT05158244: Study of Multiple Oral Doses of PF-07081532 in Adult Participants With Type 2 Diabetes Mellitus
Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MULTIPLE ORAL DOSES OF PF-07081532 IN ADULT PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus
Obesity
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-12-15
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a Phase 1, randomized, placebo-controlled, double-blind (investigator- and participant-blinded), sponsor-open study of PF-07081532. Study participants will receive the investigational product or placebo every day for 42 days.

The purpose of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of multiple oral doses of PF-07081532 in participants with inadequately controlled type 2 diabetes mellitus, on metformin and optionally in non-diabetic participants with obesity.


Eligibility criteria: Inclusion Criteria:

* Females of non childbearing potential;
* Patients with T2DM, inadequately controlled with metformin;
* HbA1c ≥7.0% to ≤10.5% (for T2DM); HbA1c \<6.5% (for non-diabetic obese, if enrolled)
* Total body weight \>50 kg (110 lbs)
* BMI ≥24.5 to ≤45.5 kg/m2 (T2DM), BMI \>30.5 to ≤45.5 kg/m2 (for non-diabetic obese)

Exclusion Criteria

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, psychiatric, neurological, dermatological, or allergic disease;
* Medical history of T2DM (for non-diabetic obese participants, if enrolled);
* Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes;
* Evidence or history of clinically significant cardiovascular disease;
* Any malignancy not considered cured;
* Acute pancreatitis or history of chronic pancreatitis;
* Acute gallbladder disease;
* Any condition possibly affecting drug absorption;
* Personal or family history of MTC or MEN2;
* Medical or psychiatric condition that may increase the risk of study participation;
* Any vaccination within the 1 week prior to admission to the CRU;
* Previous administration with an investigational drug within 30 days or 5 half-lives preceding first dose;
* Known prior participation in a trial involving PF-07081532;
* A positive urine drug screen at screening or admission;
* Positive testing at screening for HIV, HBsAg, HBcAb, HBsAb or HCVAb;
* Positive COVID-19 test at screening or admission;
* Supine BP ≥160 mm Hg (systolic) or ≥100 mm Hg (diastolic);
* 12-lead ECG clinically relevant abnormalities that may affect participant safety or interpretation of study results;
* Participants with ANY of the following abnormalities in clinical laboratory tests: \*AST or ALT level ≥1.5x ULN;

  * Total bilirubin level ≥1.5x ULN;
  * TSH\> ULN;
  * Fasting C-peptide \<0.8 ng/mL;
  * Serum calcitonin \> ULN;
  * Amylase \> ULN;
  * Lipase \> ULN;
  * eGFR \<60 mL/min/1.73m2 (per MDRD equation);
  * FPG \>270 mg/dL
* History of alcohol abuse, binge drinking and/or any illicit drug use or dependence within 6 months of Screening;
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing;
* History of sensitivity to heparin or heparin induced thrombocytopenia;
* Known intolerance to any GLP-1R agonist.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (All Causalities)
timeFrame: Baseline up to at least 28 days after last dose of study intervention (77 days)
measure: Number of Participants With Treatment-emergent Adverse Events (Treatment Related)
timeFrame: Baseline up to at least 28 days after last dose of study intervention (77 days)
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline up to 7-14 days after last dose of study drug (maximum: 56 days)
measure: Number of Participants With Pre-specified Categorical Post-Baseline Vital Signs Data
timeFrame: Baseline up to 14 days after last dose of study intervention (maximum: 56 days)
measure: Number of Participants With Pre-specified Categorical Post-Baseline Electrocardiogram (ECG) Data
timeFrame: Baseline up to 14 days after last dose of study intervention (maximum: 56 days)
Secondary outcomes:
measure: Area Under the Concentration-Time Profile From 0 to 24 Hours (AUC24) of PF-07081532 on Day 1 and Day 42
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42
measure: Maximum Observed Plasma Concentration (Cmax) of PF-07081532 on Day 1 and Day 42
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42
measure: Time to Reach Cmax (Tmax) of PF-07081532 on Day 1 and Day 42
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42
measure: Terminal Half-life (t1/2) of PF-07081532 on Day 42
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 42
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: