PF-06291874 Multiple Ascending Dose Study In Type 2 Diabetes Mellitus Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01856595
First received: May 14, 2013
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of PF-06291874 in Type 2 Diabetes patients.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: PF-06291874
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1, Placebo-Controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Escalating Oral Doses Of PF-06291874 In Adults With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0,2,4,6,8,12,19,24 hours postdose, Days 1 and 14; also 36,48,72 hours postdose Day 14 (Cohorts 1A-4A and 1B only) ] [ Designated as safety issue: No ]
  • Area under the Concentration-Time Curve (AUC) [ Time Frame: 0,2,4,6,8,12,19,24 hours postdose, Days 1 and 14; also 36,48,72 hours postdose Day 14 (Cohorts 1A-4A and 1B only) ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: 0,2,4,6,8,12,19,24 hours postdose, Days 1 and 14; also 36,48,72 hours postdose Day 14 (Cohorts 1A-4A and 1B only) ] [ Designated as safety issue: No ]
  • Apparent Oral Clearance (CL/F) [ Time Frame: 0,2,4,6,8,12,19,24 hours postdose, Days 1 and 14; also 36,48,72 hours postdose Day 14 (Cohorts 1A-4A and 1B only) ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: 0,2,4,6,8,12,19,24 hours postdose, Days 1 and 14; also 36,48,72 hours postdose Day 14 (Cohorts 1A-4A and 1B only) ] [ Designated as safety issue: No ]
  • Apparent Volume of Distribution (Vz/F) [ Time Frame: 0,2,4,6,8,12,19,24 hours postdose, Days 1 and 14; also 36,48,72 hours postdose Day 14 (Cohorts 1A-4A and 1B only) ] [ Designated as safety issue: No ]
  • Mean daily Glucose [ Time Frame: Days -1, 14 and 28 (cohorts 5A, 2B and 3B only) at 0,0.25,0.5,1,1.5,2,3,4,6,10,12,15,19,24 hrs ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • glucose AUC0-4 following mixed meal tolerance test [ Time Frame: Days -1, 14 and 28 (cohorts 5A, 2B and 3B only): 0-4 hours ] [ Designated as safety issue: No ]
  • insulin AUC0-4 following mixed meal tolerance test [ Time Frame: Days -1, 14 and 28 (cohorts 5A, 2B and 3B only): 0-4 hours ] [ Designated as safety issue: No ]
  • c-peptide AUC0-4 following mixed meal tolerance test [ Time Frame: Days -1, 14 and 28 (cohorts 5A, 2B and 3B only): 0-4 hours ] [ Designated as safety issue: No ]
  • glucagon AUC0-4 following mixed meal tolerance test [ Time Frame: Days -1, 14 and 28 (cohorts 5A, 2B and 3B only): 0-4 hours ] [ Designated as safety issue: No ]
  • fasting plasma glcuose [ Time Frame: Days -1, 2, 3, 7, 11, 14, 15, 21 (cohorts 5A, 2B and 3B only) and 28 (cohorts 5A, 2B and 3B only) ] [ Designated as safety issue: No ]
  • lipid panel [ Time Frame: Days -1, 7, 14, 21 (cohorts 5A, 2B and 3B only) and 28 (cohorts 5A, 2B and 3B only) ] [ Designated as safety issue: No ]

Enrollment: 117
Study Start Date: May 2013
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-06291874 Drug: PF-06291874
The dosing schedule is 5, 15, 50 and 150 mg QD for 14 days for the first 4 cohorts in Part A. The dosing schedule for the first cohort in Part B is 15 mg QD for 14 days. Doses for part A cohort 5 and Part B cohorts 2 and 3 are TBD QD for 28 days.
Placebo Comparator: Placebo Drug: Placebo
Placebo tablets will be administered QD in each of the cohorts for 14 days (Part A cohorts 1-4 and Part B cohort 1) or 28 days (Part A cohort 5 and Part B cohorts 2 and 3).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and female subjects of non-childbearing potential between the ages of 18 and 70 years, inclusive of age at the time of the screening visit.

Female subjects of non-childbearing potential must meet at least one of the following criteria:

  1. Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum FSH level within the laboratory's reference range for postmenopausal females;
  2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  3. Have medically confirmed ovarian failure.
  4. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

    • Body Mass Index (BMI) of 18.0 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
    • An informed consent document signed and dated by the subject.
    • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

PART A ONLY: Subjects treated with metformin monotherapy for at least 3 months at the time of the screening visit; and have been on a stable dose of metformin for at least 6 weeks prior to the first dose of study drug on Day 1. Subjects must be taking a minimum total metformin daily dose of least 1000 mg. Subjects treated with a dipeptidyl peptidase-4 inhibitor (DPP-4i), a sulfonylurea or a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) in combination with metformin may be eligible if washed off the DPP-4i, sulfonylurea or SGLT-2i for a minimum of 4 weeks prior to dosing. Subjects being washed off a DPP-4i, sulfonylurea or SGLT-2i will still need to meet the fasting glucose requirements as defined in the Inclusion Criteria.

PART B ONLY: Subjects treated with metformin plus a sulfonylurea for at least 3 months at the time of the screening visit; and have been on a stable dose of metformin and a sulfonylurea for at least 6 weeks prior to first dose of study drug on Day 1. Subjects must be taking a minimum total metformin daily dose of least 1000 mg and a total daily dose of sulfonylurea that is at least the minimum recommended starting dose found in the product label. Subjects treated with a DPP-4i or SGLT-2i in combination with metformin and a sulfonylurea may be eligible if washed off the DPP-4i or SGLT-2i for a minimum of 4 weeks before dosing.

Exclusion Criteria:

  • History of Type 1 diabetes mellitus or secondary forms of diabetes.
  • One or more self-reported hypoglycemic episodes of severe intensity within 3 months of screening; or two or more self-reported hypoglycemic episodes of severe intensity within the last 6 months.
  • Recent [ie, within six (6) months prior to screening] evidence or medical history of unstable concurrent disease such as: clinically significant hematological, endocrine,pulmonary, gastrointestinal (including severe gastroparesis), cardiovascular, hepatic, psychiatric, neurologic, or clinically significant allergic disease (excluding treated and untreated seasonal allergies at time of dosing). Subjects who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 4 weeks prior to screening) doses of medications may be included as well (for example, a subject with hypercholesterolemia on appropriate treatment is eligible).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01856595

Locations
United States, California
Pfizer Investigational Site
Anaheim, California, United States, 92801
Pfizer Investigational Site
Chula Vista, California, United States, 91911
United States, Florida
Pfizer Investigational Site
South Miami, Florida, United States, 33143
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01856595     History of Changes
Other Study ID Numbers: B4801003
Study First Received: May 14, 2013
Last Updated: March 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 29, 2014