Skip to main content
OpenTrials
Completed

NCT Number: NCT00899470

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

19 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Mds Pharma Services

Lincoln, Nebraska, 68502, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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

Other names: Onglyza

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

Other names: Onglyza, Glucophage

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

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

Primary outcomes

  1. Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)

    Time frame: 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

    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.

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

    Time frame: 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

    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.

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

    Time frame: 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

    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.

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

    Time frame: 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

    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.

  5. Metformin Mean Cmax

    Time frame: 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

    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.

  6. Metformin Mean AUC (0-T)

    Time frame: 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

    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.

  7. Metformin Mean AUC(0-INF)

    Time frame: 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

    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.

  8. Metformin T-half and T-max

    Time frame: 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

    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.

Secondary outcomes

  1. BMS-510849 Mean Cmax

    Time frame: 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

    Cmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.

  2. BMS-510849 Mean AUC (0-T)

    Time frame: 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

    AUC (0-T) for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administration as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.

  3. BMS-510849 Mean AUC (0-INF)

    Time frame: 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

    AUC (0-T)= for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.

  4. BMS-510849 Mean T-half and T-max

    Time frame: 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

    T-half and Tmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administerd as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.

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

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

    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

  6. Number of Participants With Laboratory Marked Abnormalities

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

    High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Leukocytes: <0.9 x LLN/ >1.2 x ULN; blood urea nitrogen (BUN): >1.1 x ULN; creatinine: >1.33 x BL; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN; creatinine kinase (CK): >1.5 x ULN; urine blood=use ≥2 x BL if value ≥2+ or BL1+

  7. Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities

    Time frame: Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3

    PR interval, QRS complex, width of QRS, QT interval, and QT corrected for heart rate adjusting for heart rate using either Bazett formula or Fridericia formula were measured. ECG abnormalities were judged to be of medical importance by the Investigator.

  8. Number of Participants With Clinically Relevant Vital Sign Abnormalities

    Time frame: Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3

    Mean systolic and diastolic blood pressure, heart rate, respiration, and temperature were assessed.Vital sign abnormalities abnormalities were judged to be of medical importance by the Investigator.

  9. Number of Participant With Clinically Relevant Physical Examination Abnormalities

    Time frame: Screen, Period 1 Day -1, prior to discharge

    A physical examination was conducted which included height and weight measurements, from which the Body Mass Index was determined. Physical examination abnormalities were judged to be of medical importance by the Investigator.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 500 mg Metformin Immediate Release (IR) Tablet Relative to 2.5 mg Saxagliptin Tablet and 500 mg Metformin IR Tablet Co-administered to Healthy Subjects in a Fasted and in a Fed State

Important dates

Study start
2009
Primary completion
2009
Study completion
2009
First posted
May 12, 2009
Registry last updated
Jun 1, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.