A Phase 1 Study In Japanese Subjects With Type 2 Diabetes Mellitus As Monotherapy

NCT02292433 | Completed Phase 1 Results

• 1 other identifier: B1621018
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Study B1621018 will assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Two Dose Levels of Pf-04937319 in Japanese Subjects with Type 2 Diabetes Mellitus As Monotherapy

Conditions

Type 2 Diabetes Mellitus

Keywords

Phase 1; type 2 diabetes; monotherapy; PF-04937319

Outcome Measures

Primary Outcomes (14)

• Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

  Baseline up to 14 days after the last dose of study drug (minimum 8 weeks to maximum of 17 weeks)

• Number of Participants With Protocol Defined Hypoglycaemic Adverse Events (HAEs)

  A hypoglycemic event (HAE) was identified by characteristic symptoms or blood glucose levels. HAE was defined as 1 of the given definitions: 1) Characteristic symptoms of HAE with no home glucose monitoring performed where clinical picture included prompt resolution with food intake, subcutaneous glucagon, or intravenous glucose; 2) Characteristic symptoms of HAE with home glucose monitoring measurement of less than or equal to (=\<) 70 milligram per deciliter (mg/dL) using sponsor-provided, plasma-referenced, home glucometers (or central laboratory); 3) any glucose value =\<49 mg/dL using sponsor-provided, plasma-referenced, home glucometers (or central laboratory) with or without accompanying symptoms.

  Baseline up to 14 days after the last dose of study drug (minimum 8 weeks to maximum of 17 weeks)

• Maximum Observed Plasma Concentration (Cmax) on Day 1 for PF-04937319

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1

• Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 for PF-04937319

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1

• Area Under the Concentration-Time Curve (AUC24) From Time Zero to 24 Hour on Day 1 for PF-04937319

  AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24).

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post-dose on Day 1

• Maximum Observed Plasma Concentration (Cmax) on Day 7 for PF-04937319

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7

• Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 for PF-04937319

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7

• Area Under the Concentration-Time Curve (AUC24) From Time Zero to 24 Hour on Day 7 for PF-04937319

  AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24).

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7

• Pre-dose Plasma Concentration (Ctrough) on Day 7 for PF-04937319

  Ctrough is the concentration prior to study drug administration.

  0 hour (pre-dose) on Day 7

• Average Plasma Concentration (Cav) on Day 7 for PF-04937319

  Cav is the average plasma concentration during the 0 to 24 hour time period.

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7

• Apparent Oral Clearance on Day 7 for PF-04937319

  Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. It is calculated as the total oral daily dose divided by AUC24, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours.

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7

• Terminal Half-Life (t1/2) on Day 7 for PF-04937319

  Terminal half-life is the time measured for the plasma concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (\*) 2/k el, where 'k el' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7

• Apparent Volume of Distribution on Day 7 for PF-04937319

  Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the oral bioavailability. It is calculated as the total oral daily dose divided by AUC24\* k el, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours and terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7

• Accumulation Ratio (Rac) on Day 7 for PF-04937319

  Rac is based on AUC24. It is the ratio of AUC24 of Day 7 and AUC24 of Day 1, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours.

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7

Secondary Outcomes (16)

• Maximum Observed Plasma Concentration (Cmax) on Day 1 for PF-06455349

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1

• Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 for PF-06455349

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1

• Area Under the Concentration-Time Curve (AUC24) From Time Zero to 24 Hour on Day 1 for PF--06455349

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1

• Metabolite to Parent Ratio for AUC24 (MRAUC24) on Day 1

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1

• Maximum Observed Plasma Concentration (Cmax) on Day 7 for PF--06455349

  0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7

Study Arms (2)

PF-04937319

EXPERIMENTAL

PF-04937319 Split dose

Drug: PF-04937319 high dose; Drug: PF-04937319 low dose

Placebo

PLACEBO COMPARATOR

Placebo split dose

Drug: Placebo

Interventions

PF-04937319 high dose DRUG

tablets, 150 mg with breakfast plus 100 mg with lunch, 7 days

PF-04937319

PF-04937319 low dose DRUG

tablets, 50 mg with breakfast plus 50 mg with lunch, 7 days

PF-04937319

Placebo DRUG

tablets, breakfast plus lunch, 7 days

Placebo

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with type 2 diabetes, on diet/exercise therapy only or background therapy with 1 oral anti-diabetic agent (excluding Actos)

You may not qualify if:

• Patients with cardiovascular event
• Patients with diabetic complications
• Female subjects who are pregnant or planning to become pregnant
• Subjects with unstable medical conditions (eg, hypertension)

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

P-one Clinic, Keikokai Medical Corporation

Hachioji-shi, Tokyo, 192-0071, Japan

Location

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide

Condition Hierarchy (Ancestors)

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

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
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2014
• First Posted: November 17, 2014
• Study Start: January 1, 2015
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 15, 2016
• Results First Posted: March 15, 2016

Record last verified: 2016-02

Locations

JP (1)