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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01365091
First received: May 16, 2011
Last updated: June 4, 2014
Last verified: June 2014
  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 AstraZeneca:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01365091

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

Additional Information:
No publications provided

Responsible Party: AstraZeneca
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: June 4, 2014
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
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014