Saxagliptin Triple Oral Therapy

A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IIIb Study to Evaluate Efficacy and Safety of Saxagliptin in Combination With Metformin and Sulfonylurea in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control With Combination of Metformin and Sulfonylurea

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01128153

Enrollment

257

Registered

2010-05-21

Start date

2010-06-30

Completion date

2011-06-30

Last updated

2012-08-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes

Keywords

Type 2 Diabetes, Inadequate Glycaemic Control, Saxagliptin, Metformin, Sulfonylurea, Triple Oral Therapy

Brief summary

The purpose of this study is to determine whether the addition of saxagliptin to a patient's combination treatment of metformin and sulfonylurea for a 24 week period will provide better control of the patient's type 2 diabetes and will be well tolerated.

Detailed description

A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IIIb Study to Evaluate Efficacy and Safety of Saxagliptin in Combination with Metformin and Sulfonylurea in Subjects with Type 2 Diabetes who have Inadequate Glycaemic Control with Combination of Metformin and Sulfonylurea

Interventions

DRUGSaxagliptin

5 mg tablet once daily for 24 weeks to be taken orally

DRUGPlacebo

tablet once daily for 24 weeks to be taken orally

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Written Informed Consent * Males or females with type 2 diabetes with inadequate glycaemic control (HbA1c \> or = 7% and \< or = 10%) despite being on combination of metformin and sulfonylurea for at least 8 weeks prior to Visit 1 * BMI \< or = 40 kg/m2

Exclusion criteria

* Symptoms of poorly controlled diabetes including but not limited to marked polyuria and marked polydipsia with \> 10% weight loss in 3 months prior to entry, or other signs and symptoms * History of diabetic ketoacidosis or hyperosmolar non-ketotic coma * Current or prior use within 3 months of Visit 1 of insulin, DDP4 inhibitor, GLP-1 analogues, and/or other oral anti-diabetic agents (other than metformin or sulfonylurea) * Treatment with CYP3A4 inducers and/or potent CYP3A4/5 inhibitor * Estimated CrCl \< 60 ml/min at Visit 2 * CHF (NYHA class III or IV) and/or LVEF \<40% * Active liver disease and/or significant abnormal liver function defined as AST and/or ALT \> 3 x ULN and/or bilirubin \> 2.0 mg/dL at Visit 2. * Creatine kinase \> or = 10 x ULN at Visit 2

Design outcomes

Primary

Measure	Time frame	Description
Change in HbA1c From Baseline to Week 24, Last Observation Carried Forward (LOCF)	From Baseline to Week 24 weeks	Adjusted Mean Change in HbA1c from baseline to Week 24 using analysis of covariance model

Secondary

Measure	Time frame	Description
Change in 2-hour Postprandial Glucose (PPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mg/dL]	From Baseline to Week 24	Adjusted Mean Change in 2-hour PPG from baseline to Week 24 using analysis of covariance model
Change in 2-hour Postprandial Glucose (PPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mmol/L]	From Baseline to Week 24	Adjusted Mean Change in 2-hour PPG from baseline to Week 24 using analysis of covariance model
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mg/dL]	From Baseline to Week 24	Adjusted Mean Change in fasting plasma glucose from baseline to Week 24 using analysis of covariance
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mmol/L]	From Baseline to Week 24	Adjusted Mean Change in FPG from baseline to Week 24 using analysis of covariance model
Proportion of Participants Achieving a Therapeutic Response: HbA1c Less Than 7% at Week 24, Last Observation Carried Forward (LOCF)	From Baseline to Week 24	Number of participants achieving a glycaemic response defined as HbA1c less than 7% at Week 24

Countries

Australia, Canada, India, South Korea, Thailand, United Kingdom

Participant flow

Recruitment details

Participants were recruited to the study from 35 centres in 6 countries (Australia, United Kingdom, Canada, Korea, India and Thailand). Participants were recruited between June 2010 and December 2010.

Pre-assignment details

Participants were screened over 2 week period. 383 participants enrolled; 126 excluded (11 declined, 114 did not meet eligibility criteria, 1 lost to follow up).

Participants by arm

Arm	Count
SAXAGLIPTIN Saxagliptin 5 mg tablet once daily for 24 weeks to be taken orally	129
PLACEBO Placebo tablet once daily for 24 weeks to be taken orally	128
Total	257

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	3
Overall Study	Condition under investigation worsened	8	7
Overall Study	Developed discontinuation criteria	1	1
Overall Study	Incorrect enrolment to study	2	1
Overall Study	Protocol Violation	2	0
Overall Study	Withdrawal by Subject	2	3

Baseline characteristics

Characteristic	SAXAGLIPTIN	PLACEBO	Total
2-hour Postprandial glucose	14.94 mmol/L STANDARD_DEVIATION 4.263	14.74 mmol/L STANDARD_DEVIATION 3.869	14.84 mmol/L STANDARD_DEVIATION 4.064
2-hour Postprandial Glucose	269.18 mg/dL STANDARD_DEVIATION 76.814	265.6 mg/dL STANDARD_DEVIATION 69.713	267.39 mg/dL STANDARD_DEVIATION 73.22
Age Continuous	57.2 years STANDARD_DEVIATION 9.55	56.8 years STANDARD_DEVIATION 11.49	57.0 years STANDARD_DEVIATION 10.54
BMI	29.4 kg/m2 STANDARD_DEVIATION 5.26	29.1 kg/m2 STANDARD_DEVIATION 4.93	29.2 kg/m2 STANDARD_DEVIATION 5.09
Fasting Plasma Glucose	9.00 mmol/L STANDARD_DEVIATION 2.626	155.45 mg/dL STANDARD_DEVIATION 38.37	158.84 mg/dL STANDARD_DEVIATION 43.125
HbA1c	8.38 % STANDARD_DEVIATION 0.856	8.19 % STANDARD_DEVIATION 0.832	8.28 % STANDARD_DEVIATION 0.848
Race/Ethnicity, Customized Asian	70 Participants	71 Participants	141 Participants
Race/Ethnicity, Customized White	59 Participants	57 Participants	116 Participants
Region of Enrollment Australia	25 Participants	25 Participants	50 Participants
Region of Enrollment Canada	10 Participants	10 Participants	20 Participants
Region of Enrollment India	35 Participants	34 Participants	69 Participants
Region of Enrollment Korea, Republic of	25 Participants	24 Participants	49 Participants
Region of Enrollment Thailand	8 Participants	10 Participants	18 Participants
Region of Enrollment United Kingdom	26 Participants	25 Participants	51 Participants
Sex: Female, Male Female	49 Participants	54 Participants	103 Participants
Sex: Female, Male Male	80 Participants	74 Participants	154 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	53 / 129	65 / 128
serious Total, serious adverse events	3 / 129	7 / 128

Outcome results

Primary

Change in HbA1c From Baseline to Week 24, Last Observation Carried Forward (LOCF)

Adjusted Mean Change in HbA1c from baseline to Week 24 using analysis of covariance model

Time frame: From Baseline to Week 24 weeks

Population: Full Analysis Set which included all participants randomised to the study who received at least 1 dose of investigational product and who had a non-missing baseline value and at least 1 post-baseline measure. The full analysis set follows intention-to-treat principle.

Arm	Measure	Value (MEAN)
Arm 1 - SAXAGLIPTIN	Change in HbA1c From Baseline to Week 24, Last Observation Carried Forward (LOCF)	-0.74 percent
Arm 2 - PLACEBO	Change in HbA1c From Baseline to Week 24, Last Observation Carried Forward (LOCF)	-0.08 percent

p-value: <0.000195% CI: [-0.86, -0.47]ANCOVA

Secondary