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

NCT04305587 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C3991002
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Diabetes Mellitus Type 2

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• Area Under the Curve From Time 0 to 24 Hours (AUC24) Post Dose for PF-07081532

  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

  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

  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

  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

  Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)

Study Arms (4)

Active Obesity

EXPERIMENTAL

Part B

Other: Placebo; Drug: Clopidogrel

Placebo Obesity

PLACEBO COMPARATOR

Part B

Other: Placebo; Drug: Clopidogrel

Active T2DM

EXPERIMENTAL

Parts A and C

Drug: PF-07081532

Placebo T2DM

PLACEBO COMPARATOR

Parts A and C

Drug: PF-07081532

Interventions

PF-07081532 DRUG

Investigational Drug once daily for up to 42 days; multiple ascending dose design.

Active T2DM; Placebo T2DM

Placebo OTHER

Placebo once daily for up to 42 days.

Active Obesity; Placebo Obesity

Clopidogrel DRUG

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.

Also known as: Plavix

Active Obesity; Placebo Obesity

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Type 1 Diabetes or secondary forms of diabetes.
• Obese (as indicated by screening BMI) non-diabetic adults.
• Type 1 or Type 2 Diabetes or secondary forms of diabetes.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

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

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind (investigator- and participant-blind), sponsor-open
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: March 16, 2020
• Primary Completion: July 14, 2021
• Study Completion: July 14, 2021
• Last Updated: February 5, 2024
• Results First Posted: February 5, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)