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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

May 16, 2011
June 4, 2014
June 2011
November 2011   (final data collection date for primary outcome measure)
  • 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
  • Evidence of bioequivalence (BE) on single-dose pharmacokinetic parameters maximum observed concentration (Cmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: In the 48 hours after dosing ] [ Designated as safety issue: No ]
  • Evidence of bioequivalence (BE) on single-dose pharmacokinetic parameters time of maximum observed concentration (Tmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: In the 48 hours after dosing ] [ Designated as safety issue: No ]
  • Evidence of bioequivalence (BE) on single-dose pharmacokinetic parameters AUC(INF) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: In the 48 hours after dosing ] [ Designated as safety issue: No ]
    area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
  • Evidence of bioequivalence (BE) on single-dose pharmacokinetic parameters AUC(0-T) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: In the 48 hours after dosing ] [ Designated as safety issue: No ]
    area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))
  • Evidence of bioequivalence (BE) on single-dose pharmacokinetic parameters half-life (T-HALF) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: In the 48 hours after dosing ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01365091 on ClinicalTrials.gov Archive Site
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.
  • Number of participants with adverse events [ Time Frame: Adverse events collected from Day 1 of Period 1 through study discharge (study duration: approximately 46 days) ] [ Designated as safety issue: Yes ]
    Adverse events tabulated by system organ class, preferred term and formulation
  • Levels of Active metabolite of Saxagliptin, 5-Hydroxy Saxagliptin (BMS-510849) [ Time Frame: In the 48 hours after dosing, respectively ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Bioequivalence Study of Fixed-dose Combinations and Coadministered Individual Tablets of Saxagliptin/Metformin-Brazil
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

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Type 2 Diabetes Mellitus
  • 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
  • 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 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).

    Interventions:
    • Drug: Saxagliptin/metformin fixed-dose combination (FDC)
    • Drug: Saxagliptin
    • Drug: Metformin extended-release (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).

    Interventions:
    • Drug: Saxagliptin/metformin fixed-dose combination (FDC)
    • Drug: Saxagliptin
    • Drug: Metformin extended-release (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).

    Interventions:
    • Drug: Saxagliptin
    • Drug: Saxagliptin/Metformin FDC
    • Drug: Metformin
  • 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).

    Interventions:
    • Drug: Saxagliptin
    • Drug: Saxagliptin/Metformin FDC
    • Drug: Metformin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
112
November 2011
November 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Brazil
 
NCT01365091
CV181-162
No
AstraZeneca
AstraZeneca
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
AstraZeneca
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP