Bioequivalence Study of Fixed Dose Combination of 2.5 mg Saxagliptin/850 mg Metformin Tablet Relative to 2.5 mg Onglyza and 850 mg Glucophage Tablets Co-Administered

NCT01068743 | Completed Phase 1 Results

• 1 other identifier: CV181-121
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To demonstrate bioequivalence of a 2.5 mg saxagliptin/850 mg metformin fixed dose combination (FDC) tablet relative to the 2.5 mg saxagliptin tablet and 850 mg metformin (Glucophage Marketed by Merck-Serono) tablet co-administered to healthy subjects in the fasted and fed condition.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])

  PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax)

  PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• Metformin PK Parameter AUC(0-inf)

  PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• Metformin PK Parameter Cmax

  PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

Secondary Outcomes (7)

• 5-hydroxy Saxagliptin PK Parameter AUC(0-inf)

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• 5-hydroxy Saxagliptin PK Parameter Cmax

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• 5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2)

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax)

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

Other Outcomes (6)

• Saxagliptin PK Parameter AUC(0-t)

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• Saxagliptin PK Parameter T1/2

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

• Saxagliptin PK Parameter Tmax

  Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

Study Arms (4)

Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting)

OTHER

A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fasted condition.

Drug: saxagliptin; Drug: metformin

Arm B (saxagliptin 2.5 mg + metformin 850 mg FDC; Fasting)

OTHER

A single oral dose of 2.5-mg saxagliptin/850-mg metformin fixed dose combination (FDC) administered in the fasted condition.

Drug: saxagliptin + metformin (FDC tablet)

Arm C (saxagliptin 2.5 mg + metformin 850 mg; Fed)

OTHER

A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fed condition.

Drug: saxagliptin; Drug: metformin

Arm D (saxagliptin 2.5 mg + metformin 850 mg FDC; Fed)

OTHER

A single oral dose of 2.5-mg saxagliptin/850-mg metformin FDC administered in the fed condition.

Drug: saxagliptin + metformin (FDC tablet)

Interventions

saxagliptin DRUG

Tablets, Oral, 2.5 mg, once daily, single dose

Also known as: Onglyza

Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting); Arm C (saxagliptin 2.5 mg + metformin 850 mg; Fed)

metformin DRUG

Tablets, Oral, 850 mg, once daily, single dose

Also known as: Glucophage

Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting); Arm C (saxagliptin 2.5 mg + metformin 850 mg; Fed)

saxagliptin + metformin (FDC tablet) DRUG

Tablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose

Arm B (saxagliptin 2.5 mg + metformin 850 mg FDC; Fasting); Arm D (saxagliptin 2.5 mg + metformin 850 mg FDC; Fed)

Eligibility Criteria

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

You may qualify if:

• Men and women ages 18 to 55 inclusive
• Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 32 kg/m\^2, inclusive. BMI = weight (kg)/ \[height (m)\]\^2

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 a dipeptidyl peptidase-IV (DPP4) inhibitor or related compound
• History of allergy or intolerance to metformin or other similar acting agents
• Prior exposure to saxagliptin
• Prior exposure to metformin within 3 months of study drug administration
• Estimated creatinine clearance (Clcr) 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: February 1, 2010
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 8, 2015
• Results First Posted: February 8, 2012

Record last verified: 2015-03

Locations

US (1)