Bioequivalence Study of Fixed-dose Combinations and Coadministered Individual Tablets of Saxagliptin/Metformin-Brazil

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01365091
First received: May 16, 2011
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

To demonstrate the bioequivalence of saxagliptin and metformin in a saxagliptin, 5-mg/metformin extended-release (XR), 500-mg, fixed-dose combination (FDC) tablet with saxagliptin, 5-mg and metformin, 500-mg XR tablets administered together in both the fasted and fed states. In addition, to demonstrate the bioequivalence of saxagliptin and metformin in a saxagliptin, 5-mg/metformin XR, 1000-mg, FDC tablet with saxagliptin, 5-mg and metformin, 1000-mg XR tablets administered together in both the fasted and fed states.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Saxagliptin/metformin fixed-dose combination (FDC)
Drug: Saxagliptin
Drug: Metformin extended-release (XR)
Drug: Saxagliptin/Metformin FDC
Drug: Metformin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Bioequivalence Study of Fixed Dose Combinations of Saxagliptin/Metformin Extended Release (XR) Relative to Co-administration of the Individual Components in Healthy Subjects in the Fasted and Fed States

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets [ Time Frame: Days 1, 2, and 3 of Periods 1 and 2 ] [ Designated as safety issue: No ]
  • AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets [ Time Frame: Days 1, 2, and 3 of Periods 1 and 2 ] [ Designated as safety issue: No ]
    AUC=Area under the concentration-time curve

  • AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets [ Time Frame: Days 1, 2, and 3 of Periods 1 and 2 ] [ Designated as safety issue: No ]
    AUC=Area Under the Concentration-time Curve


Secondary Outcome Measures:
  • Number of Participants With Death as Outcome and Serious Adverse Events (SAEs) [ Time Frame: Continuously, from screening through Day 1 to within 30 days of drug discontinuation on Day 1 ] [ Designated as safety issue: Yes ]
    SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.


Enrollment: 112
Study Start Date: June 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Treatments A,B/B,A

Period 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg fixed-dose combination (FDC) in the fasted state (Treatment A), followed by a washout period of at least 7 days. Then, participants received single oral doses of saxagliptin, 5-mg, and metformin extended-release (XR), 500-mg, tablets together in the fasted state (Treatment B). Followed by a washout period of at least 4 days.

Period 2: Participants received single oral doses of saxagliptin, 5-mg and metformin XR, 500-mg tablets together in the fasted state (Treatment B), followed by a washout period of at least 7 days. Then, participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg FDC, in the fasted state (Treatment A).

Drug: Saxagliptin/metformin fixed-dose combination (FDC)
Tablet, oral, 5 mg/500 mg FDC, once on Day 1 only, 1 day
Other Name: Onglyza/Glucophage extended release (XR)
Drug: Saxagliptin
Tablet, oral, 5 mg, once on Day 1 only, 1 day
Other Name: Onglyza
Drug: Metformin extended-release (XR)
Tablet, oral, 500 mg, once on Day 1 only, 1 day
Other Name: Glifage XR
Experimental: Arm 2: Treatments C,D/D,C

Period 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg fixed-dose combination (FDC), in the fed state (Treatment C), followed by a washout period of at least 7 days. Then, participants received a single oral dose of saxagliptin, 5-mg, and metformin extended-release (XR), 500-mg tablets together in the fed state (Treatment D). Followed by a washout period of at least 4 days.

Period 2: Participants received a single oral dose of saxagliptin, 5-mg and metforminXR, 500-mg tablets together in the fed state (Treatment D), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg FDC, in the fed state (Treatment C).

Drug: Saxagliptin/metformin fixed-dose combination (FDC)
Tablet, oral, 5 mg/500 mg FDC, once on Day 1 only, 1 day
Other Name: Onglyza/Glucophage extended release (XR)
Drug: Saxagliptin
Tablet, oral, 5 mg, once on Day 1 only, 1 day
Other Name: Onglyza
Drug: Metformin extended-release (XR)
Tablet, oral, 500 mg, once on Day 1 only, 1 day
Other Name: Glifage XR
Experimental: Arm 3: Treatments E, F/F,E

Period 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg fixed-dose combination (FDC), in the fasted state (Treatment E), followed by a washout period of at least 7 days. Participants received single oral doses of saxagliptin, 5-mg and metformin extended-release (XR), 1000-mg tablets together in the fasted state (Treatment F). Followed by a washout period of at least 4 days.

Period 2: Participants received single oral doses of saxagliptin, 5- mg and metformin XR, 1000-mg tablets together in the fasted state (Treatment F), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg FDC, in the fasted state (Treatment E).

Drug: Saxagliptin
Tablet, oral, 5 mg, once on Day 1 only, 1 day
Other Name: Onglyza
Drug: Saxagliptin/Metformin FDC
Tablet, Oral, 5 mg/1000 mg FDC, once on Day 1 only, 1 day
Other Name: Onglyza/Glucophage XR
Drug: Metformin
Tablet, oral, 1000 mg, once on Day 1 only, 1 day
Other Name: Glifage XR
Experimental: Arm 4: Treatments G,H/H,G

Period 1: Participants received a single oral dose of saxagliptin , 5 mg/metformin, 1000 mg fixed-dose combination (FDC), in the fed state (Treatment G), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5-mg and metformin extended-release (XR), 1000-mg tablets together in the fed state (Treatment H). Followed by a washout period of at least 4 days.

Period 2: Participants received a single oral dose of saxagliptin, 5-mg and metformin XR, 1000-mg tablets together in the fed state (Treatment H), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg FDC, in the fed state (Treatment G).

Drug: Saxagliptin
Tablet, oral, 5 mg, once on Day 1 only, 1 day
Other Name: Onglyza
Drug: Saxagliptin/Metformin FDC
Tablet, Oral, 5 mg/1000 mg FDC, once on Day 1 only, 1 day
Other Name: Onglyza/Glucophage XR
Drug: Metformin
Tablet, oral, 1000 mg, once on Day 1 only, 1 day
Other Name: Glifage XR

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

  • Healthy men and women
  • women of childbearing potential who are using acceptable method of contraception
  • Women who are not pregnant or nursing
  • Body Mass Index (BMI) of 18 to 29.9 kg/m^2, inclusive. BMI=weight(kg)/height(m)^2.

Key Exclusion Criteria:

  • Any significant acute or chronic medical illness.
  • History of gastrointestinal (GI) disease
  • Major surgery within 4 weeks of study drug administration
  • Any GI surgery that could impact study drug absorption
  • Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within the 6 months of study drug administration.
  • Blood transfusion within 3 months of study drug administration for women and within 2 months for men
  • Inability to be venipunctured and/or tolerate venous access
  • Current smoker or recent (within 1 month) history of regular tobacco use
  • Recent (within 6 months of study drug administration) drug or alcohol abuse
  • Participation in a bioequivalence study within the last 6 months of study drug administration
  • Estimated creatinine clearance of <80 mL/min using Cockcroft-Gault formula
  • History of allergy to drug class or related compounds
  • History of allergy to metformin or other similar acting agents
  • History of any significant drug allergy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01365091

Locations
Brazil
Local Institution
Campinas, Sao Paulo, Brazil, 13073
Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01365091     History of Changes
Other Study ID Numbers: CV181-162
Study First Received: May 16, 2011
Results First Received: March 20, 2013
Last Updated: August 16, 2013
Health Authority: Brazil: Ethics Committee
Brazil: National Health Surveillance Agency

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014