To Compare the Similarity of a Combination Dapagliflozin/Metformin Tablet With the Two Drugs Administered Separately

NCT01535677 | Completed Phase 1

• 1 other identifier: D1691C00007
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomised study to compare the similarity of a combination Dapagliflozin/Metformin tablet with the two drugs administered separately under fasting and fed conditions in healthy volunteers.

Conditions

Type 2 Diabetes Mellitus

Keywords

Phase 1; healthy volunteers; cross-over study; Bioavailability; Bioequivalence; Cmax; tmax; AUC; AUC(0-t); λz; tlast

Outcome Measures

Primary Outcomes (3)

• Area under the curve over the time (AUC)

  No statistical analysis will be performed

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

• AUC from time zero to the time of last quantifiable analyte concentration (AUC(0-t))

  No statistical analysis will be performed

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

• Maximum concentration (Cmax)

  No statistical analysis will be performed

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

Secondary Outcomes (14)

• Time to reach maximum analyte concentration (tmax)

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

• Terminal rate constant (λz)

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

• Time of last quantifiable analyte concentration (tlast)

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

• Terminal half-life (t1/2)

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

• Observed maximum analyte concentration (Cmax)

  pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose

Study Arms (4)

1

EXPERIMENTAL

5 mg dapagliflozin and 850 mg Glucophage in fasted state

Drug: Dapagliflozin + Glucophage tablet fasted

2

EXPERIMENTAL

dapagliflozin/metformin (5 mg/850 mg) immediate release (IR) FDC in fasted

Drug: Dapagliflozin/metformin IR FDC tablet fasted

3

EXPERIMENTAL

5 mg dapagliflozin and 850 mg Glucophage in fed state

Drug: Dapagliflozin + Glucophage tablet fed

4

EXPERIMENTAL

dapagliflozin/metformin (5 mg/850 mg) IR FDC in fed state

Drug: Dapagliflozin/metformin IR FDC tablet fed

Interventions

Dapagliflozin + Glucophage tablet fasted DRUG

Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fasted state

1

Dapagliflozin/metformin IR FDC tablet fasted DRUG

single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fasted state

2

Dapagliflozin + Glucophage tablet fed DRUG

Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fed state

3

Dapagliflozin/metformin IR FDC tablet fed DRUG

single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fed state

4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers aged 18 to 55 years inclusive with suitable veins for cannulation or repeated vein puncture
• Male subjects should be willing to use barrier contraception ie, condoms and spermicide, from the day of dosing until at least 3 months after dosing with the investigational product
• Non-pregnant, non-lactating female subjects who if pre-menopausal are using adequate birth control eg, oral, injectable, transdermal or implanted hormonal contraceptives, vaginal contraceptive ring, intrauterine device (IUD)/intrauterine systems
• Have a body mass index (BMI) between 18.5 and 30.0 kg/m2 inclusive (ie, within 15% of normal range) and weigh at least 50 kg and no more than 100 kg.

You may not qualify if:

• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with individual safety evaluation Current smokers who smoke more than 5 cigarettes per day (or equivalent use of tobacco products) or cannot give up smoking during the study
• Excessive intake of caffeine containing drinks eg, coffee, tea, caffeine containing energy drinks and cola (more than 5 cups of coffee or equivalent per day)
• Plasma donation within one month of screening or any blood donation/blood loss \>500 mL during the 3 months prior to screening

Sponsors & Collaborators

• AstraZeneca: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Publications (1)

• Chang M, Liu X, Cui D, Liang D, LaCreta F, Griffen SC, Lubin S, Quamina-Edghill D, Boulton DW. Bioequivalence, Food Effect, and Steady-State Assessment of Dapagliflozin/Metformin Extended-release Fixed-dose Combination Tablets Relative to Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Subjects. Clin Ther. 2015 Jul 1;37(7):1517-28. doi: 10.1016/j.clinthera.2015.05.004. Epub 2015 Jun 3.

  PMID: 26048185 RESULT

Related Links

• D1691C00007\_CSR\_Synopsis
• D1691C00007\_Clinical\_Study\_Protocol

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Eva Johnsson, MD

  AstraZeneca Research and Development SE-431 83 Mölndal Sweden

  STUDY DIRECTOR

• Saeed Kahn, MBBS

  Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen St, London SE1 1YR

  PRINCIPAL INVESTIGATOR

• Mirjana Kujacic, PHD

  AstraZeneca Research and DevelopmentSE-431 83 Mölndal Sweden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2012
• First Posted: February 20, 2012
• Study Start: April 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 9, 2015

Record last verified: 2015-07

Locations

GB (1)