Efficacy and Safety of Alogliptin and Metformin Fixed-dose Combination in Patients With Type 2 Diabetes

Diabetes Mellitus Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Alogliptin and Metformin Fixed Dose Combination, Alogliptin Alone, or Metformin Alone in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01890122
• Other study ID #: SYR-322MET_303
• Secondary ID: U1111-1139-0497N
• Status: Completed
• Phase: Phase 3
• First received: June 26, 2013
• Last updated: December 8, 2015
• Start date: September 2013
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Malaysia: Ministry of HealthSouth Korea: Institutional Review BoardChina: Food and Drug AdministrationChina: Ethics CommitteeChina: Ministry of HealthTaiwan: Food and Drug Administration, Ministry of Health and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of alogliptin and metformin fixed-dose combination (FDC) as compared with alogliptin alone or metformin alone on Type 2 Diabetes Mellitus (T2DM).

Description:

The drug being tested in this study is a fixed-dose combination tablet of alogliptin and metformin to treat people who have diabetes. This study will look at glycemic control in people who take alogliptin and metformin FDC compared with alogliptin or metformin alone. The study will enroll approximately 640 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Alogliptin 12.5 mg twice daily (BID)

• Metformin HCL 500 mg BID

• Alogliptin 12.5 mg and Metformin HCL 500 mg FDC BID

• Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.

All participants will be asked to take 2 tablets and 1 capsule twice a day at the same time each day throughout the study. All participants will be asked to record any hypoglycemic events in a diary. This multi-centre trial will be conducted in China, South Korea, and Malaysia. The overall time to participate in this study is 34 weeks. Participants will make 11 visits to the clinic.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 651
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. Has a historical diagnosis of T2DM.

4. Male or female and aged 18 to 75 years, inclusive.

5. Body mass index (BMI) between 20 and 45 kg/m^2, inclusive.

6. A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

7. Is experiencing inadequate glycemic control defined as HbA1c concentration between 7.5% and 10%, inclusive, and has been treated with diet and exercise for at least 2 months prior to Screening. (Exception: a participant who has received any other diabetic therapy for less than 7 days in total within the 2 months prior to the screening, can be included).

8. If male, has a hemoglobin >12 g/dL (>120 g/L) at Screening or if female, has a hemoglobin >10 g/dL (>100 g/L) at Screening.

9. If male, has a serum creatinine <1.5 mg/dL at Screening or if female, has a serum creatinine <1.4 mg/dL at Screening, and estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m^2 based on calculation using the Modification of Diet in Renal Disease (MDRD) at Screening.

10. Willing and able to monitor their own blood glucose concentrations using a home glucose monitor and complete a subject diary.

Exclusion Criteria:

1. Participated in another clinical study within 90 days prior to Screening.

2. Received any investigational compound within 30 days prior to Randomization.

3. Received a dipeptidyl peptidase-4 (DPP-4) inhibitor within 3 months prior to screening.

4. History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.

5. History of treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery.

6. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.

7. Chronic pancreatitis and/or history of acute pancreatitis.

8. Systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg at Screening.

9. History of any hemoglobinopathy or diagnosis of chronic anemia.

10. New York Heart Association Class III or IV heart failure. (Participants who are stable at Class I or II and are currently treated, are candidates for the study.)

11. History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.

12. History of any cancer, other than squamous cell or basal cell carcinoma of the skin, which has not been in full remission for at least 5 years prior to Screening. Participants with a history of treated cervical intraepithelial neoplasia [CIN] I or CIN II are allowed.

13. Significant clinical sign or symptom of hepatopathy, acute or chronic hepatitis, human immunodeficiency virus or alanine aminotransferase (ALT) is 2.5 times above upper limit of normal value.

14. History of angioedema in association with use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB).

15. History of hypersensitivity or allergies to any DPP-4 inhibitor and/or metformin or related compounds.

16. Has used oral or systemically injected glucocorticoids (including intra-articular injection) or has used weight-loss drugs within 2 months prior to Screening. (Inhaled or topical corticosteroids were allowed.)

17. History of alcohol or substance abuse within 2 years prior to Screening.

18. Has used medicine for weight loss within 60 days prior to Screening (such as Xenical, Sibutramine, Phenylpropanolamine or similar nonprescription drugs).

19. History of organ transplantation.

20. Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

21. Has, in the judgment of the investigator, any major illness or debility that may prohibit the participant from completing the study.

22. If female, is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

Drug:
• Alogliptin
Alogliptin tablets.
• Metformin HCl
Metformin capsules.
• Alogliptin and Metformin fixed-dose combination (FDC)
Aloglptin and metformin FDC tablets.
• Alogliptin placebo
Alogliptin placebo-matching tablets.
• Metformin placebo
Metformin placebo-matching capsules.
• Alogliptin and metformin FDC placebo
Alogliptin and metformin FDC placebo-matching tablets.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

China,  Korea, Republic of,  Malaysia,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 26 (or Early Termination) in Glycosylated Hemoglobin (HbA1c)	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 26 or early termination.	Baseline and Week 26	No
Secondary	Change From Baseline in HbA1c Over Time		Baseline and Weeks 4, 8, 12, 16 and 20	No
Secondary	Change From Baseline in Fasting Plasma Glucose Over Time		Baseline and Weeks 4, 8, 12, 16, 20 and 26	No
Secondary	Time to hyperglycemic rescue event	Rescue is defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 7 days of first sample: -After > 1 week of treatment but prior to Week 4 visit: A single fasting plasma glucose (FPG) =275 mg/dL (=15.27 mmol/L); -From the Week 4 but prior to the Week 8 visit: A single FPG =250 mg/dL (=13.88 mmol/L); -From the Week 8 visit but prior to the Week 12 visit: A single FPG =225 mg/dL (=12.49 mmol/L); -From the Week 12 visit through the end-of-treatment visit (week 26): HbA1c =8.5% and =0.5% reduction in HbA1c from baseline.	From the date of randomization through Week 26	No
Secondary	Percentage of Participants Meeting Rescue Criteria	Rescue is defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 7 days of first sample: -After > 1 week of treatment but prior to Week 4 visit: A single fasting plasma glucose (FPG) =275 mg/dL (=15.27 mmol/L); -From the Week 4 but prior to the Week 8 visit: A single FPG =250 mg/dL (=13.88 mmol/L); -From the Week 8 visit but prior to the Week 12 visit: A single FPG =225 mg/dL (=12.49 mmol/L); -From the Week 12 visit through the end-of-treatment visit (week 26): HbA1c =8.5% and =0.5% reduction in HbA1c from baseline.	Weeks 4, 8, 12, 16 and 26	No
Secondary	Percentage of Participants With Marked Hyperglycemia	Marked hyperglycemia is defined as a fasting plasma glucose level = 200 mg/dL (11.1 mmol/L).	Weeks 4, 8, 12, 16, 20 and 26	No
Secondary	Change From Baseline in Body Weight Over Time		Baseline and Weeks 12 and 26	No
Secondary	Percentage of Participants With Glycosylated Hemoglobin = 6.5%	Clinical response at Week 26 will be assessed by the percentage of participants with HbA1c less than or equal to 6.5%.	Week 26	No
Secondary	Percentage of Participants With Glycosylated Hemoglobin = 7.0%	Clinical response at Week 26 will be assessed by the percentage of participants with HbA1c less than or equal to 7%.	Week 26	No
Secondary	Percentage of Participants With Glycosylated Hemoglobin = 7.5%	Clinical response at Week 26 will be assessed by the percentage of participants with HbA1c less than or equal to 7.5%.	Week 26	No
Secondary	Percentage of Participants With a Decrease in Glycosylated Hemoglobin = 0.5%	Clinical response at Week 26 will be assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.	Baseline and Week 26	No
Secondary	Percentage of Participants With a Decrease in Glycosylated Hemoglobin = 1.0%	Clinical response at Week 26 will be assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.0%.	Baseline and Week 26	No
Secondary	Percentage of Participants With a Decrease in Glycosylated Hemoglobin = 1.5%	Clinical response at Week 26 will be assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.	Baseline and Week 26	No
Secondary	Percentage of Participants With a Decrease in Glycosylated Hemoglobin = 2.0%	Clinical response at Week 26 will be assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%.	Baseline and Week 26	No

External Links

•   The Alogliptin-Metformin Fixed Dose Combination (KAZANO) were recently approved in the United States (US) on 25 January 2013.