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

NCT00897390 | Completed Phase 1 Results

• 1 other identifier: CV181-092
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To demonstrate bioequivalence of a 2.5 mg saxagliptin/1000 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 1000 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 (10)

• Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF])

  Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T])

  Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax)

  Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF)

  Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax)

  Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Metformin PK Parameter AUC(INF)

  Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Metformin PK Parameter AUC(0-T)

  Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Metformin PK Parameter Cmax

  Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Metformin PK Parameter T-HALF

  Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• Metformin PK Parameter Tmax

  Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Secondary Outcomes (10)

• BMS-510849 PK Parameter AUC(INF)

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• BMS-510849 PK Parameter AUC(0-T)

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• BMS-510849 PK Parameter Cmax

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• BMS-510849 PK Parameter T-Half

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

• BMS-510849 PK Parameter T-Max

  pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Study Arms (4)

Arm A

OTHER

Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions

Drug: Saxagliptin; Drug: Metformin IR (glucophage)

Arm B

OTHER

Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions

Drug: Saxagliptin + Metformin IR (FDC)

Arm C

OTHER

Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal

Drug: Saxagliptin; Drug: Metformin IR (glucophage)

Arm D

OTHER

Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Drug: Saxagliptin + Metformin IR (FDC)

Interventions

Saxagliptin DRUG

Tablet, Oral, 2.5 mg, Once Daily, 1 week

Also known as: Onglyza

Arm A; Arm C

Metformin IR (glucophage) DRUG

Tablets, Oral, 1000 mg, Once Daily, 1 week

Also known as: Glucophage

Arm A; Arm C

Saxagliptin + Metformin IR (FDC) DRUG

Tablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week

Also known as: Onglyza, Glucophage

Arm B; Arm D

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: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: May 21, 2015
• Results First Posted: January 21, 2011

Record last verified: 2015-05

Locations

US (1)