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Completed

NCT Number: NCT05158244

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

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.

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Key information

Conditions

Type 2 Diabetes Mellitus Body Weight Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Qps-Mra, Llc

South Miami, Florida, 33143, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-07081532

Drug

Study Drug, once daily for 42 days

Placebo

Drug

Placebo, once daily for 42 days

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events (All Causalities)

    Time frame: Baseline up to at least 28 days after last dose of study intervention (77 days)

    An adverse event (AE) was any untoward medical occurrence in clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs.

  2. Number of Participants With Treatment-emergent Adverse Events (Treatment Related)

    Time frame: Baseline up to at least 28 days after last dose of study intervention (77 days)

    A treatment related adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study drug, considered related to the study drug (assessed by the investigator [Yes/No]). A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs.

  3. Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

    Time frame: Baseline up to 7-14 days after last dose of study drug (maximum: 56 days)

    Following laboratory parameters analyzed for laboratory examination: hemoglobin (HGB); hematocrit; erythrocytes; erythrocytes (Ery.) mean corpuscular volume; Ery. mean corpuscular HGB; Ery. mean corpuscular HGB concentration; platelets; leukocytes; lymphocytes; neutrophils; basophils; eosinophils; monocytes; bilirubin; direct bilirubin; indirect bilirubin; aspartate aminotransferase; alanine aminotransferase; gamma glutamyl transferase; alkaline phosphatase; albumin; urea nitrogen; creatinine; urate; cholesterol; high density lipoprotein (HDL) cholesterol; sodium; potassium; chloride; calcium; bicarbonate; thyroxine; free; thyrotropin; creatine kinase; amylase; triacylglycerol lipase; triglycerides; pH; urine glucose; ketones; urine protein; urine hemoglobin; urobilinogen; urine bilirubin; nitrite; leukocyte esterase; urine erythrocytes; urine leukocytes; epithelial cells; casts; and bacteria.

  4. Number of Participants With Pre-specified Categorical Post-Baseline Vital Signs Data

    Time frame: Baseline up to 14 days after last dose of study intervention (maximum: 56 days)

    Pre-specified categorical criteria included: supine systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg), supine SBP increase from baseline greater or equal to (>=) 30 mmHg, supine SBP decrease from baseline >=30 mmHg, supine diastolic blood pressure (DBP) <50 mmHg, supine DBP increase from baseline >=20 mmHg, supine DBP decrease from baseline >=20 mmHg, supine pulse rate <40 beats per minutes (bpm), and supine pulse rate greater than (>) 120 bpm. Supine BP was measured with the participant's arm supported at the level of the heart, and recorded to the nearest mmHg after approximately 5 minutes of rest.

  5. Number of Participants With Pre-specified Categorical Post-Baseline Electrocardiogram (ECG) Data

    Time frame: Baseline up to 14 days after last dose of study intervention (maximum: 56 days)

    Triplicate 12-lead ECGs were collected using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. Pre-specified categorical criteria included: PR interval greater or equal to 300 msec, PR interval %Chg>=25/50% (%Chg>=25/50% denotes baseline >200 msec and >=25% increase or baseline less than or equal to [<=] 200 msec and >=50% increase), QRS interval >=140 msec, QRS interval increase from baseline >=50%, QT interval corrected using Fridericia's formula (QTcF) >450 msec and <=480 msec, QTcF >480 msec and <=500 msec, QTcF >500 msec, QTcF increase from baseline >30 msec and <=60 msec, and QTcF increase from baseline >60 msec.

Secondary outcomes

  1. Area Under the Concentration-Time Profile From 0 to 24 Hours (AUC24) of PF-07081532 on Day 1 and Day 42

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42

    AUC24 of PF-07081532 were determined by Linear/Log trapezoidal method on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

  2. Maximum Observed Plasma Concentration (Cmax) of PF-07081532 on Day 1 and Day 42

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42

    Cmax of PF-07081532 were observed directly from data from time 0 to 24 hours on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

  3. Time to Reach Cmax (Tmax) of PF-07081532 on Day 1 and Day 42

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42

    Tmax of PF-07081532 were observed directly from data as time of first occurrence on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

  4. Terminal Half-life (t1/2) of PF-07081532 on Day 42

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 42

    t1/2 of PF-07081532 was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Dec 15, 2021
Registry last updated
Aug 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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