A Study to Learn How Different Amounts of PF-06954522 Are Tolerated and Act in Adults With Type 2 Diabetes Mellitus

NCT06279234 | Completed Phase 1 FDA Drug

• 2 other identifiers: C4001002NCT06279234
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple escalating oral doses of PF-06954522 in adult participants with inadequately controlled type 2 diabetes mellitus (T2DM) on metformin (Part A) and optionally in non-diabetic participants with obesity (Part B).

Conditions

Type 2 Diabetes Mellitus (T2DM); Obesity

Keywords

T2DM; Obesity; PF-06954522; Rosuvastatin; Midazolam; Omeprazole; DDI; C4001002

Outcome Measures

Primary Outcomes (5)

• Number of Participants Reporting Adverse Events

  Baseline through Week 14

• Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities

  Baseline through Week 14

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  Baseline through Week 14

• Number of Participants With Clinically Significant Change From Baseline in 12-Lead ECGs

  Baseline through Week 14

• Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS)

  Baseline through Week 14

Secondary Outcomes (7)

• Maximum Observed Plasma Concentration (Cmax)

  Part A: Days -1, 1, 14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24, 30. Part A & B: Days -1, 1, 28, 49 & 56. Days 7, 14, 21, 35, 42, 57 & 58. Part C: Period 3 Day 3 & Period 5 Day 28

• Area Under the Curve from Time Zero to end of dosing interval (AUCtau)

  Part A: Days -1, 1, 14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24, 30. Part A & B: Days -1, 1, 28, 49 & 56. Days 7, 14, 21, 35, 42, 57, 58. Part C: Period 3 Day 3 & Period 5 Day 28

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Part A: Days -1, 1, 14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24 & 30. Part A & B: Day -1, 1 28, 49 & 56. Days 7, 14, 21, 35, 42, 57 & 58. Part C: Period 3 Day 3 & Period 5 Day 28

• Plasma Decay Half-Life (t1/2)

  Part A: Day -1, 1,14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24 & 30. Part A & B: Day -1, 1, 28, 49 & 56. Days 7, 14, 21, 35, 42, 57 & 58. Part C: Period 3 Day 3 & Period 5 Day 28

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)

  Part A: Day 28. Part A & B: Day 56

Study Arms (3)

Part A

EXPERIMENTAL

Multiple doses of PF 06954522 or placebo daily for up to 8 weeks in adult participants with T2DM in up to 7 cohorts.

Drug: Placebo; Drug: PF-06954522

Part B (Optional)

EXPERIMENTAL

Multiple doses of PF 06954522 or placebo daily for up to 8 weeks in non-diabetic adult participants with obesity in up to 3 cohorts.

Drug: Placebo; Drug: PF-06954522

Part C (Optional)

EXPERIMENTAL

An 8-period multiple-dose assessment of the effect of PF-06954522 on rosuvastatin, midazolam, and omeprazole PK in healthy adult participants for up to 14 weeks in healthy adult participants.

Drug: Rosuvastatin; Drug: Midazolam; Drug: Omeprazole; Drug: PF-06954522

Interventions

Placebo DRUG

Oral tablet

Part A; Part B (Optional)

Rosuvastatin DRUG

Oral tablet

Part C (Optional)

Midazolam DRUG

Oral suspension

Part C (Optional)

Omeprazole DRUG

Oral tablet

Part C (Optional)

PF-06954522 DRUG

Oral tablet

Part A; Part B (Optional); Part C (Optional)

Eligibility Criteria

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

You may qualify if:

• Female participants of non-childbearing potential and males between the ages of 18 and 70 years, inclusive, at the time of signing the ICD.
• Part A only: Diagnosis of Diabetes - Participants enrolling with T2DM must have a clinical history of T2DM and be taking metformin monotherapy as their only anti-hyperglycemic treatment. Metformin dose must be at least 500 mg per day and must be stable, defined as no change in the treatment, including dose, for at least 2 months prior to the screening visit.
• Part C only: Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• HbA1c
• Part A only: For participants enrolling with T2DM: HbA1c ≥7.0% and ≤10.5% at screening (confirmed by a single repeat, if necessary).
• Part B and C only: For participants enrolling as non-diabetic with obesity (Part B), or healthy (Part C): HbA1c \<6.5% at screening.
• BMI
• All participants must have a total body weight \>50 kg (110 lbs).
• Parts A and B only: Stable body weight, defined as \<5 kg change (per participant report) for 90 days prior to screening
• Part A only: For participants enrolling with T2DM: BMI ≥24.5 to ≤45.5 kg/m2.
• Part B only: For participants enrolling as non-diabetic with obesity: BMI \>30.5 to ≤45.5 kg/m2
• Part C only: For participants enrolling as healthy: BMI 20-30.5 kg/m2
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, psychiatric, neurological, dermatological, or allergic disease (including drug allergies but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Parts A and B only: Participants with T2DM (Part A) or obesity (Part B) are allowed. Participants who have chronic conditions other than T2DM and obesity (eg, hypercholesterolemia or hypertension) but are controlled by either diet or stable doses of 2 or fewer medications may be included (eg, a participant with hypercholesterolemia on appropriate treatment is eligible).
• Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency).
• History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
• Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes.
• Parts B and C only: Participants enrolling as non-diabetic with obesity (Part B) or healthy (Part C) may not have medical history of T2DM.
• Evidence or history of clinically significant cardiovascular disease. In particular, history of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II IV heart failure, or transient ischemic attack within 6 months of screening.
• Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin); a participant is considered cured if there has been no evidence of cancer recurrence in the previous 5 years.
• Acute pancreatitis or history of chronic pancreatitis.
• Acute gallbladder disease.
• Parts A and B only: A response of 'yes' to question 4 or 5 or on any behavioral question on the C-SSRS at Screening or Day -1 in the study. In addition, participants deemed by the investigator to be at significant risk of suicidal or violent behavior should be excluded.
• Personal or family history of MTC or MEN2, or participants with suspected MTC per the investigator's judgement.
• Any medical or psychiatric condition including recent (within the past year) history of: suicidal ideation/behavior, major depressive disorder, schizophrenia, bipolar disorder; or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
• Use of prescription or nonprescription drugs and dietary and herbal supplements that are BCRP, MDR1/P-gp, or OATP inhibitors is prohibited within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention; use of moderate or strong inhibitors or inducers of CYP3A, UGT1A1, or UGT1A3 is prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
• Part A and B: Use of certain concomitant medication that are unlikely to interfere with the study results may be allowed. However, use of prescription or nonprescription drugs and dietary and herbal supplements that are sensitive CYP1A2, CYP2C19, CYP3A, BCRP, MDR1/P-gp, OATP1B3, or UGT1A1 substrates is prohibited post Day -1.

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 Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

Rosuvastatin Calcium; Midazolam; Omeprazole

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

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Pyridines; Benzimidazoles

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: February 28, 2024
• Study Start: February 20, 2024
• Primary Completion: April 11, 2025
• Study Completion: April 11, 2025
• Last Updated: June 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)