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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Saxagliptin/Metformin FDC; Drug: Metformin; Drug: Saxagliptin/metformin fixed-dose combination (FDC); Drug: Saxagliptin; Drug: Metformin extended-release (XR)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01365091

CV181-162

Details and patient eligibility

About

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.

Enrollment: 112 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

112 participants in 4 patient groups

Arm 1: Treatments A,B/B,A

Experimental group

Description:

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).

Treatment:

Drug: Metformin extended-release (XR)

Drug: Saxagliptin

Drug: Saxagliptin/metformin fixed-dose combination (FDC)

Arm 2: Treatments C,D/D,C

Experimental group

Description:

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).

Treatment:

Drug: Metformin extended-release (XR)

Drug: Saxagliptin

Drug: Saxagliptin/metformin fixed-dose combination (FDC)

Arm 3: Treatments E, F/F,E

Experimental group

Description:

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).

Treatment:

Drug: Saxagliptin

Drug: Metformin

Drug: Saxagliptin/Metformin FDC

Arm 4: Treatments G,H/H,G

Experimental group

Description:

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).

Treatment:

Drug: Saxagliptin

Drug: Metformin

Drug: Saxagliptin/Metformin FDC