Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus (0431-061)

NCT00511108 | Completed Phase 1 Results

• 3 other identifiers: 0431-061MK0431-0612007_530
• Study Type: interventional
• Target: 211
• Locations: 0 countries
• Sites: N/A

Brief Summary

A clinical study to determine the safety, efficacy and mechanism of action of sitagliptin alone and in combination with pioglitazone, in patients with type 2 diabetes mellitus who have inadequate glycemic (blood sugar) control.

Conditions

Type 2 Diabetes Mellitus (T2DM)

Keywords

Type 2 Diabetes Mellitus (T2DM)

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment

  Glucagon concentration was measured at 9 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, and 180 minutes. Total AUC was calculated over 3 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.

  Baseline and 12 weeks

• Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment

  Static sensitivity is a measure of the effect of glucose on beta cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. Percent change from baseline was calculated as the difference between index of static sensitivities at Week 12 and at baseline with respect to the index of static sensitivity at baseline times 100.

  Baseline and 12 weeks

Secondary Outcomes (1)

• Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment

  Baseline and 12 weeks

Study Arms (4)

1

EXPERIMENTAL

Arm 1: drug

Drug: Comparator: sitagliptin phosphate; Drug: Comparator: placebo to pioglitazone

2

ACTIVE COMPARATOR

Arm 2: active comparator

Drug: Comparator: pioglitazone; Drug: Comparator: placebo to sitagliptin

3

EXPERIMENTAL

Arm 3: drug + active comparator

Drug: Comparator: sitagliptin phosphate; Drug: Comparator: pioglitazone

4

PLACEBO COMPARATOR

Arm 4: placebo comparator

Drug: Comparator: placebo to pioglitazone; Drug: Comparator: placebo to sitagliptin

Interventions

Comparator: sitagliptin phosphate DRUG

sitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily.

1; 3

Comparator: pioglitazone DRUG

pioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.

2; 3

Comparator: placebo to pioglitazone DRUG

pioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.

1; 4

Comparator: placebo to sitagliptin DRUG

sitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.

2; 4

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has type 2 diabetes mellitus
• Male
• Female that is highly unlikely to become pregnant
• Patient is not on an antihyperglycemic agent (AHA) (hemoglobin A1c \[A1C\] 7-10%) or on oral single AHA or low-dose combination therapy (A1C 6.5-9.0%)

You may not qualify if:

• Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis
• Patient has required insulin therapy within the past 12 weeks
• Patient is on or has been taking a Peroxisome Proliferator-Activated Receptor-gamma (PPAR -gamma) agent (i.e. Thiazolidinediones \[TZDs\]) within the prior 12 weeks of the screening visit.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Alba M, Ahren B, Inzucchi SE, Guan Y, Mallick M, Xu L, O'Neill EA, Williams-Herman DE, Kaufman KD, Goldstein BJ. Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function. Diabetes Obes Metab. 2013 Dec;15(12):1101-10. doi: 10.1111/dom.12145. Epub 2013 Jul 19.

  PMID: 23782502 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2007
• First Posted: August 3, 2007
• Study Start: July 11, 2007
• Primary Completion: February 24, 2009
• Study Completion: February 24, 2009
• Last Updated: May 12, 2017
• Results First Posted: March 5, 2010

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share