Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants

NCT01068717 | Completed Phase 1 Results

• 1 other identifier: CV181-118
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

To demonstrate the bioequivalence of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet to that of 2.5-mg saxagliptin (Onglyza) and 500-mg metformin (Glucophage, marketed in Canada by Sanofi-Aventis) tablets coadministered to healthy participants in the fasted and fed states.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (8)

• Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

• Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

• Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

• Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

• AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

• AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

• AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

• Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States

  Days 1, 2, and 3 of Periods 1, 2, 3, and 4

Secondary Outcomes (4)

• Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation

  Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4

• Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results

  At screening visit, at Day -1 of Periods 1 through 4, and at discharge

• Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results

  At screening visit, Day -1 of Period 1, and at study discharge

• Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate

  At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge.

Study Arms (4)

Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)

OTHER

Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fasted state

Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)

Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fasted state)

OTHER

Single oral dose of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet administered in the fasted state

Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state)

Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)

OTHER

Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fed state

Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)

Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fed state)

OTHER

Single oral dose of saxagliptin, 2.5 mg/metformin, 500 mg, FDC tablet administered in the fed state

Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state)

Interventions

Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state) DRUG

Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week

Also known as: Onglyza™, Glucophage™

Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)

Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state) DRUG

Tablets, oral, 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC), once daily, 1 week

Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fasted state)

Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state) DRUG

Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week

Also known as: Onglyza™, Glucophage™

Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)

Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state) DRUG

Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin FDC, once daily, 1 week

Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fed state)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, aged 18 to 55 years, inclusive
• Healthy participants as determined by a lack of clinically significant deviation from normal in medical history, physical examination, electrocardiograms, and clinical laboratory determinations
• Body Mass Index of 18 to 32 kg/m\^2, inclusive

You may not qualify if:

• Any significant acute or chronic medical illness
• Current or recent (within 3 months) gastrointestinal disease
• Any major surgery within 4 weeks of study drug administration
• History of allergy to DPP-4 inhibitors or related compounds
• History of allergy or intolerance to metformin or other similar acting agents
• Previous exposure to saxagliptin
• Exposure to metformin within 3 months pervious to study drug administration
• Estimated creatinine clearance of \<80 mL/min using the Cockcroft Gault formula

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Ppd Development, Lp

Austin, Texas, 78744, United States

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

saxagliptin; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Boaz Hirschberg
• Organization: AstraZeneca Pharmaceuticals

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  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: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2010
• First Posted: February 15, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 12, 2015
• Results First Posted: October 21, 2011

Record last verified: 2015-04

Locations

US (1)