Clinical trial NCT01890122: Efficacy and Safety of Alogliptin and Metformin Fixed-Dose Combination in Participants With Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2013-07-01
Enrollment: 647
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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).

Detailed 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 participant and study doctor during the study (unless there is an urgent medical need):

* Alogliptin 12.5 mg twice daily (BID)
* Metformin hydrochloride (HCl) 500 mg BID
* Alogliptin 12.5 mg and Metformin HCl 500 mg FDC BID
* Placebo (dummy inactive pill) - this is a tablet/capsule 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-center trial will be conducted in China, South Korea, Taiwan and Malaysia. The overall time to participate in this study is 34 weeks. Participants will make 11 visits to the clinic.

Eligibility criteria: 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 Type 2 diabetes mellitus (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 glycosylated hemoglobin (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 mm Hg and/or diastolic blood pressure \>110 mm Hg 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.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 (or Early Termination)
timeFrame: Baseline and Week 26 (or Early termination)
Secondary outcomes:
measure: Change From Baseline in HbA1c at Weeks 4, 8, 12, 16 and 20
timeFrame: Baseline and Weeks 4, 8, 12, 16 and 20
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20 and 26
measure: Time to Hyperglycemic Rescue Event
timeFrame: From the date of randomization through Week 26
measure: Percentage of Participants Requiring Hyperglycemic Rescue
timeFrame: Baseline up to Week 26
measure: Percentage of Participants With Marked Hyperglycemia
timeFrame: Baseline up to Week 26
measure: Change From Baseline in Body Weight at Weeks 12 and 26
timeFrame: Baseline and Weeks 12 and 26
measure: Percentage of Participants With Glycosylated Hemoglobin ≤6.5%
timeFrame: Week 26
measure: Percentage of Participants With Glycosylated Hemoglobin ≤7.0%
timeFrame: Week 26
measure: Percentage of Participants With Glycosylated Hemoglobin ≤7.5%
timeFrame: Week 26
measure: Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥0.5%
timeFrame: Baseline and Week 26
measure: Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥1.0%
timeFrame: Baseline and Week 26
measure: Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥1.5%
timeFrame: Baseline and Week 26
measure: Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥2.0%
timeFrame: Baseline and Week 26
Other outcomes:
Locations:
city: Beijing
country: China
state: Beijing
city: Fuzhou
country: China
state: Fujian
city: Xiamen
country: China
state: Fujian
city: Guangzhou
country: China
state: Guangdong
city: Nanning
country: China
state: Guangxi
city: Guiyang
country: China
state: Guizhou
city: Hengshui
country: China
state: Hebei
city: Shijiazhuang
country: China
state: Hebei
city: Shiyan
country: China
state: Hubei
city: Wuhan
country: China
state: Hubei
city: Changsha
country: China
state: Hunan
city: Yueyang
country: China
state: Hunan
city: Changzhou
country: China
state: Jiangsu
city: Nanjing
country: China
state: Jiangsu
city: Suzhou
country: China
state: Jiangsu
city: Nanchang
country: China
state: Jiangxi
city: Changchun
country: China
state: Jilin
city: Shenyang
country: China
state: Liaoning
city: Xi'an
country: China
state: Shanxi
city: Chengdu
country: China
state: Sichuan
city: Wenzhou
country: China
state: Zhejiang
city: Beijing
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Goyang-si
country: Korea, Republic of
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Johor Bahru
country: Malaysia
state: Johor
city: Alor Setar
country: Malaysia
state: Kedah Darul Aman
city: Alor Setar
country: Malaysia
state: Kedah
city: Kubang Kerian
country: Malaysia
state: Kelantan
city: Nilai
country: Malaysia
state: Negeri Sembilan
city: Seremban
country: Malaysia
state: Negeri Sembilan
city: Tampin
country: Malaysia
state: Negeri Sembilan
city: Bagan Serai
country: Malaysia
state: Perak
city: Ipoh
country: Malaysia
state: Perak
city: Petaling Jaya
country: Malaysia
state: Selangor
city: Shah Alam
country: Malaysia
state: Selangor
city: Putrajaya
country: Malaysia
state: WIlayah Persekutuan
city: Kaohsiung
country: Taiwan
city: New Taipei City
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: