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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 1000 mg Metformin Immediate Release (IR) Tablet Relative to 2.5 mg Saxagliptin Tablet and 1000 mg Metformin IR Tablet Co-administered to Healthy Subjects in a Fasted and in a Fed State

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00897390
• Other study ID #: CV181-092
• Status: Completed
• Phase: Phase 1
• First received: May 8, 2009
• Last updated: May 4, 2015
• Start date: June 2009
• Est. completion date: July 2009

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 19 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Saxagliptin
Tablet, Oral, 2.5 mg, Once Daily, 1 week
• Metformin IR (glucophage)
Tablets, Oral, 1000 mg, Once Daily, 1 week
• Saxagliptin + Metformin IR (FDC)
Tablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week

Locations

Country	Name	City	State
United States	Mds Pharma Services	Lincoln	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	BMS-510849 PK Parameter AUC(INF)	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, 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	No
Secondary	BMS-510849 PK Parameter AUC(0-T)	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, 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	No
Secondary	BMS-510849 PK Parameter Cmax	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, 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	No
Secondary	BMS-510849 PK Parameter T-Half	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from their respective 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	No
Secondary	BMS-510849 PK Parameter T-Max	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, 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	No
Secondary	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs	An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is 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, or is an important medical event.	AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject's participation in the study.	Yes
Secondary	AEs of Special Interest	See Outcome Measure 16 for a definition of AEs. AEs of clinical interest for saxagliptin were defined as those relating to the following:skin disorders, infection-related AEs (system organ class [SOC]: Infections and Infestations), thrombocytopenia, lymphopenia, hypoglycemia, cardiovascular AEs indicative of acute cardiovascular events, localized edema, fractures, pancreatitis, and AEs of hypersensitivity.	AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days).	Yes
Secondary	Number of Participants With Marked Laboratory Abnormalities (MA)	Laboratory abnormalities=any result that is clinically significant, met the definition of an SAE, required discontinuation or interruption of study drug, or required specific corrective therapy. Upper normal (UN)/lower normal (LN) values: leukocytes UN, 11.40x10^3 c/uL; absolute neutrophils/bands LN, 1.500x10^3 c/uL; aspartate aminotransferase UN, 48 U/L; alanine aminotransferase UN, 67 U/L; blood urea nitrogen UN, 20.0 mg/dL; creatine kinase UN, 350 U/L; lactate dehydrogenase UN, 249 U/L.	Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.	Yes
Secondary	Number of Participants With Marked Urinalysis Abnormalities	Protein, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Glucose, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Blood, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). White Blood Cell (WBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). Red Blood Cell (RBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). (The '+' is a normal lab result and refers to the magnitude of the finding.)	Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.	Yes
Secondary	Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities	12-lead Electrocardiogram (ECG), Vital Sign (body temperature, respiratory rate, seated blood pressure and heart rate), and Physical Finding Abnormalities reported by investigator as AEs.	At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form