4-Week, Multiple-dose, Dose-escalating Study In Patients With Type 2 Diabetes

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF MULTIPLE ESCALATING ORAL DOSES OF PF-06882961 IN ADULT SUBJECTS WITH TYPE 2 DIABETES MELLITUS

This is a dose-escalating study in patients with Type 2 diabetes on metformin. Participants will receive an investigational product or placebo for 28 days.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: PF-06882961; Drug: PF-06882961; Drug: PF-06882961; Drug: PF-06882961; Drug: PF-06882961; Drug: PF-06882961; Drug: PF-06882961; Drug: PF-06882961

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
  • Florida
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
    • South Miami, Florida, United States, 33143
      • Qps-Mra,Llc
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences Clinical Kansas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes treated with a stable dose of metformin at least 500 mg
• HbA1c value between 7.0 and 10.5%

Exclusion Criteria:

- Type 1 diabetes or secondary forms of diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Tablet, 0 mg, twice daily, 28 days
EXPERIMENTAL: PF-06882961 30 mg	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days
EXPERIMENTAL: PF-06882961 100 mg	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days
EXPERIMENTAL: PF-06882961 300 mg	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days
EXPERIMENTAL: PF-06882961 600 mg	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days
EXPERIMENTAL: PF-06882961 dose TBD Cohort 5	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days
EXPERIMENTAL: PF-06882961 dose TBD Cohort 6	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days
EXPERIMENTAL: PF-06882961 dose TBD Cohort 7	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days
EXPERIMENTAL: PF-06882961 dose TBD Cohort 8	Drug: PF-06882961; Tablet, 15 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 50 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 150 mg twice daily, 28 days; Drug: PF-06882961; Tablet, 300 mg twice daily, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 5, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 6, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 7, 28 days; Drug: PF-06882961; Tablet, dose TBD, twice daily, Cohort 8, 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All-causality and Treatment-related Treatment-emergent Adverse Events (TEAEs)	Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent.	From baseline to up to 35 days after last dose for a total of approximately 63 days
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality	Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time [PT], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin).	From baseline to up to 14 days after last dose for a total of approximately 42 days
Number of Participants With Abnormal Vital Signs	Vital signs categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP >= 20 mmHg.	From baseline to up to 14 days after last dose for a total of approximately 42 days
Number of Participants With Abnormal Electrocardiogram (ECG) Interval	ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec. 2. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline	From baseline to up to 14 days after last dose for a total of approximately 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC24 and AUCtau of PF-06882961 on Day 1, Day 14 or 21 and Day 28	Area under the concentration-time profile from time zero to time 24 hours (AUC24) was calculated as AUCtau1 +AUCtau2, where AUCtau was area under the plasma concentration-time profile from time zero to time tau (tau1 = 0 to 10 hours and tau2=10 to 24 hours). AUCtau was determined using linear/log trapezoidal method.	0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28
Maximum Plasma Concentration (Cmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28	For BID dosing, parameters were calculated for both dosing intervals (0-10 hr = interval 1 and 10-24 hr = interval 2) and were displayed as Cmax1, Cmax2. Cmax1: maximum plasma concentration during the dosing interval τ1 =0 to 10 hours. Cmax2: maximum plasma concentration during the dosing interval τ2=10 to 24 hours.	0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1, 14 or 21, and 28
Time for Cmax (Tmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28	Time for Cmax, Cmax1 and Cmax2 (Tmax, Tmax1 and Tmax2) of PF-06293620 was observed directly from data as time of first occurrence.	0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28
Terminal Half-life (t½) of PF-06882961 on Day 28	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 28
Amount of Unchanged Drug Recovered in Urine Over 24 Hours (Ae24) of PF-06882961 on Day 28	Ae was the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval was 24 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL was the approximate specific gravity of urine.	0 to 24 hours post-dose on Day 28
Ae24 (%) of PF-06882961 on Day 28	Percent of dose recovered in urine as unchanged drug. Ae24% = 100* Ae24/Dose	0 to 24 hours post-dose on Day 28
Renal Clearance (CLr) of PF-06882961 on Day 28	CLr was calculated as Ae divided by AUCtau, where dosing interval is 24 hours.	0 to 24 hours post-dose on Day 28

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Saxena AR, Gorman DN, Esquejo RM, Bergman A, Chidsey K, Buckeridge C, Griffith DA, Kim AM. Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial. Nat Med. 2021 Jun;27(6):1079-1087. doi: 10.1038/s41591-021-01391-w. Epub 2021 Jun 14.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 25, 2018
• Primary Completion (ACTUAL): May 23, 2019
• Study Completion (ACTUAL): June 10, 2019

Study Registration Dates

• First Submitted: May 7, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (ACTUAL): May 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: C3421002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No