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

NCT05158244 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C3991003
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus; Obesity

Outcome Measures

Primary Outcomes (5)

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

  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.

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

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

  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.

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

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

  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.

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

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

  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.

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

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

  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.

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

Secondary Outcomes (4)

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

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

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

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

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

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

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

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

Study Arms (2)

PF-07081532

EXPERIMENTAL

multiple dosing, once-daily for 42 days

Drug: PF-07081532

Placebo

PLACEBO COMPARATOR

multiple dosing, once-daily for 42 days

Drug: Placebo

Interventions

PF-07081532 DRUG

Study Drug, once daily for 42 days

PF-07081532

Placebo DRUG

Placebo, once daily for 42 days

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Qps-Mra, Llc

South Miami, Florida, 33143, United States

Location

Related Publications (1)

• Buckeridge C, Tsamandouras N, Carvajal-Gonzalez S, Brown LS, Hernandez-Illas M, Saxena AR. Once-daily oral small-molecule glucagon-like peptide-1 receptor agonist lotiglipron (PF-07081532) for type 2 diabetes and obesity: Two randomized, placebo-controlled, multiple-ascending-dose Phase 1 studies. Diabetes Obes Metab. 2024 Aug;26(8):3155-3166. doi: 10.1111/dom.15643. Epub 2024 May 16.

  PMID: 38751362 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: December 15, 2021
• Study Start: December 22, 2021
• Primary Completion: June 15, 2022
• Study Completion: June 15, 2022
• Last Updated: August 12, 2024
• Results First Posted: August 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)