Bioequivalence Study of Saxagliptin and Glucophage Combination Formulations in Healthy Subjects (A)

NCT00899470 | Completed Phase 1 Results

• 1 other identifier: CV181-081
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To demonstrate bioequivalence of a 2.5 mg saxagliptin/500 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 500 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (8)

• Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)

  Cmax of single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]}

  AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])

  AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max)

  T-half and T-max for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg) or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Metformin Mean Cmax

  Cmax of single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Metformin Mean AUC (0-T)

  AUC (0-T for single-dose metformin (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Metformin Mean AUC(0-INF)

  AUC (0-INF) for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Metformin T-half and T-max

  T-half and T-max for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg), or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

Secondary Outcomes (9)

• BMS-510849 Mean Cmax

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• BMS-510849 Mean AUC (0-T)

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• BMS-510849 Mean AUC (0-INF)

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• BMS-510849 Mean T-half and T-max

  Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

• Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation

  From Day 1 through Day 45, including up to 56 days after last dose of study medication

Study Arms (4)

S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)

EXPERIMENTAL

Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M \[fasted\]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M \[fed\]) followed by S/M under fasting conditions (S/M \[fasted\]) followed by S + M under fed conditions (S + M \[fed\])

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted; Drug: Saxagliptin/Metformin, Fasting; Drug: Co-administration of Saxagliptin and Metformin IR, Fed; Drug: Saxagliptin/Metformin, Fed

S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)

EXPERIMENTAL

Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted; Drug: Saxagliptin/Metformin, Fasting; Drug: Co-administration of Saxagliptin and Metformin IR, Fed; Drug: Saxagliptin/Metformin, Fed

S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)

EXPERIMENTAL

Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted; Drug: Saxagliptin/Metformin, Fasting; Drug: Co-administration of Saxagliptin and Metformin IR, Fed; Drug: Saxagliptin/Metformin, Fed

S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)

EXPERIMENTAL

Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted; Drug: Saxagliptin/Metformin, Fasting; Drug: Co-administration of Saxagliptin and Metformin IR, Fed; Drug: Saxagliptin/Metformin, Fed

Interventions

Co-administration of Saxagliptin and Metformin IR, Fasted DRUG

Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions

Also known as: Onglyza

S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed); S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted); S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed); S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)

Saxagliptin/Metformin, Fasting DRUG

Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions

Also known as: Onglyza, Glucophage

S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed); S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted); S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed); S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)

Co-administration of Saxagliptin and Metformin IR, Fed DRUG

Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions

S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed); S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted); S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed); S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)

Saxagliptin/Metformin, Fed DRUG

Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed); S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted); S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed); S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)

Eligibility Criteria

• Age: 19 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women ages 19 to 45 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/m2, inclusive. BMI = weight (kg)/ \[height (m)\]2

You may not qualify if:

• Women of child-bearing potential (WOCBP) who are unwilling or unable to use acceptable barrier methods (condoms and spermicides) to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product
• 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 Dipeptidyl peptidase 4 (DPP4) inhibitor or related compounds
• 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 \< 80ml/min using the Cockcroft Gault formula

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Mds Pharma Services

Lincoln, Nebraska, 68502, United States

Location

Related Publications (1)

• Upreti VV, Keung CF, Boulton DW, Chang M, Li L, Tang A, Hsiang BC, Quamina-Edghill D, Frevert EU, Lacreta FP. Bioequivalence of saxagliptin/metformin immediate release (IR) fixed-dose combination tablets and single-component saxagliptin and metformin IR tablets in healthy adult subjects. Clin Drug Investig. 2013 May;33(5):365-74. doi: 10.1007/s40261-013-0075-z.

  PMID: 23549864 DERIVED

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: May 8, 2009
• First Posted: May 12, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: June 1, 2015
• Results First Posted: March 25, 2011

Record last verified: 2015-05

Locations

US (1)