Clinical trial NCT02512068: A Phase 3, Randomized, Double-blind, Parallel-group, Comparative Study and a Phase 3, Multicenter, Open-label, Long-term Study of SYR-472 (25 mg) in Patients With Type 2 Diabetes Mellitus Complicated by Severe Renal Impairment or End-stage Renal Disease
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Comparative Study and a Phase 3, Multicenter, Open-label, Long-term Study to Evaluate the Efficacy and Safety of SYR-472 When Orally Administered at a Dose of 25 mg Once Weekly in Patients With Type 2 Diabetes Mellitus Complicated by Severe Renal Impairment or End-stage Renal Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-07-30
Enrollment: 107
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of trelagliptin when administered at a dose of 25 mg once weekly using placebo as a control in patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease and inadequate glycemic control despite diet and/or exercise therapy (if given) or despite treatment with one antidiabetic drug in addition to diet and/or exercise therapy (if given); and to evaluate the long-term efficacy and safety of trelagliptin when administered at a dose of 25 mg once weekly to patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease.

Detailed description: This is a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, comparative study (Treatment Period I) and a phase 3, multicenter, open-label, long-term study (Treatment Period II) to evaluate the efficacy and safety of trelagliptin when administered orally at a dose of 25 mg once weekly to patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease and inadequate glycemic control despite diet and/or exercise therapy (if given) or despite treatment with one antidiabetic drug in addition to diet and/or exercise therapy (if given).

Eligibility criteria: Inclusion Criteria:

1. The participant has a diagnosis of type 2 diabetes mellitus.
2. The participant has a fasting C-peptide value of 0.6 ng/mL or higher at the start of the screening period (Week -6) and Week -2 of the screening period.
3. The participant has a hemoglobin value of 10.0 g/dL or higher at the start of the screening period (Week -6) and Week -2 of the screening period.
4. The participant has a Haemoglobin A1c (HbA1c) value of 7.0% or higher but less than 10.0% at Week -2 of the screening period. For participants undergoing hemodialysis (with End-stage Renal Disease \[ESRD\]), those with a glycoalbumin value of 20% or higher could be enrolled even if their HbA1c value is below 7.0% at Week -2 of the screening period.
5. \<HbA1c value of 7.0% or higher but less than 10.0% at Week -2 of the screening period\> The participant has an HbA1c value difference between the start of the screening period (Week -6) and Week -2 of the screening period within 10.0%\* of the HbA1c value at the start of the screening period (Week -6).

   \<For participants undergoing hemodialysis (with ESRD), glycoalbumin value of 20% or higher and HbA1c value of below 7.0% at Week -2 of the screening period\> The participant has a glycoalbumin difference between the start of the screening period (Week -6) and Week -2 of the screening period within 10.0%\* of the glycoalbumin value at the start of the screening period (Week -6).

   \*: rounded to one decimal place
6. The participant has been on a fixed diet and/or exercise therapy (if any) for at least 6 weeks prior to the start of the screening period (Week -6).
7. The participant meets any of the following:

   * The participant has not received any antidiabetic medications (including insulin preparations) from at least 6 weeks prior to the start of the screening period (Week -6).
   * The participant is being treated with one oral hypoglycemic drug\* starting from at least 6 weeks prior to the start of the screening period (Week -6) at a fixed dose and regimen.

     \*: any one of the following medications: mitiglinide calcium hydrate, repaglinide, acarbose, miglitol, or voglibose
   * The participant is being treated with one insulin preparation\*\* starting from at least 6 weeks prior to the start of the screening period (Week -6) at a fixed dose and regimen (≤40 units/day) of the insulin preparation.

     * Any one of the following insulin monotherapies: mixed (short-acting or rapid-acting insulin containing no more than 30% volume), intermediate-acting, or long-acting soluble insulin preparations
8. The participant is not undergoing hemodialysis or peritoneal dialysis and has severe renal impairment \[creatinine clearance (Ccr) \<30 mL/min at the start of the screening period (Week -6)\], or the participant is undergoing hemodialysis and has end-stage renal failure.
9. In the opinion of the investigator or sub-investigator, the initiation of hemodialysis or peritoneal dialysis at least within 12 weeks after starting the investigational product is not expected. \[in cases where the participant is not undergoing hemodialysis or peritoneal dialysis (patients with severe renal impairment)\]
10. The participant has been undergoing hemodialysis starting from at least 6 months prior to informed consent and, in the opinion of the investigator or sub-investigator, the participant is clinically stable. \[in cases where the participant is undergoing hemodialysis (patient with end-stage renal failure)\]
11. The participant is male or female and is aged 20 years or older at the time of informed consent.
12. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent until one month after the end of the study.
13. In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
14. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.

Exclusion Criteria:

1. The participant has clinically evident hepatic impairment \[e.g., aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 times the upper limit of normal or total bilirubin of ≥2.0 mg/dL at the start of the screening period (Week -6) or at Week -2 of the screening period\].
2. The participant has any serious cardiac diseases, cerebrovascular disorders, or serious pancreatic or hematological diseases (e.g., participants who require inpatient treatment or are hospitalized for treatment within 24 weeks prior to the start of the screening period).
3. The participant has severe ketosis, diabetic coma or precoma, type 1 diabetes, severe infection, before or after surgery, or severe external trauma.
4. The participant has hemoglobinopathy (sickle cell disease, thalassemia, etc.).
5. The participant experienced hypoglycemia (participants with a blood glucose value of ≤70 mg/dL or hypoglycemic symptoms) within 6 weeks prior to the start of the screening period or during the screening period (at least twice per week).
6. The participant has inadequately controlled hypertension.
7. For participants who are being treated with one antidiabetic agent, the participant was using at least two antidiabetic therapies on the day before 6 weeks prior to the start of the screening period (Week -6) (43 days prior to the start of the screening period).
8. The participant has malignancies.
9. The participant has a history of hypersensitivity or allergies to dipeptidyl peptidase 4 (DPP-4) inhibitors.
10. The participant has a history of gastrectomy or small intestinal resection.
11. The participant is a habitual drinker and consumes a daily average of more than 100 mL of alcohol.
12. The participant has a history of drug abuse (defined as the use of an illegal drug) or alcohol dependence.
13. The participant is required to take excluded medications during the study period.
14. The participant has previously received trelagliptin.
15. The participant received any other investigational products (including study drugs in a post-marketing clinical study) within 12 weeks prior to the start of the screening period.
16. The participant is participating in other clinical studies at the time of informed consent.
17. If female, the participant is pregnant or lactating or intending to become pregnant from the time of informed consent to within 1 month after the end of the study; or intending to donate ova during such time period.
18. The participant is an immediate family member of a study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
19. The participant is hospitalized during the screening period or is deemed as requiring hospitalization during the study period by the investigator or sub-investigator, unless the hospitalization is for short-term evaluations including complete health checkups or shunt (including shunt maintenance).
20. The participant is deemed ineligible for the study for any other reason by the investigator or sub-investigator.

Primary outcomes:
measure: Change From Baseline in HbA1c at the End of Treatment Period I
timeFrame: Baseline (Week 0) and end of Treatment Period I (Up to Week 12)
measure: Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE) Before the Start of Study Drug Administration in Treatment Period II
timeFrame: Up to Week 12
measure: Number of Participants Who Had One or More TEAE Occurred After 1st Dose of Trelagliptin 25 mg Tablet
timeFrame: Up to Week 54
Secondary outcomes:
measure: Changes From Baseline in HbA1c
timeFrame: Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)
measure: Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II
timeFrame: At the end of Treatment Period I (Up to Week 12) and Period II (Up to Week 52)
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)
measure: Change From Baseline in Glycoalbumin
timeFrame: Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)
measure: Numbers of Participants With TEAE Related to Vital Signs Before the Start of Study Drug Administration in Treatment Period II
timeFrame: Up to Week 12
measure: Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II
timeFrame: Up to Week 12
measure: Number of Participants With Markedly Abnormal Values of Clinical Laboratory Parameters Before the Start of Study Drug Administration in Treatment Period II
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Anjo
country: Japan
state: Aichi
city: Kasukabe
country: Japan
state: Aichi
city: Nagoya
country: Japan
state: Aichi
city: Toyohashi
country: Japan
state: Aichi
city: Yatomi
country: Japan
state: Aichi
city: Asahi
country: Japan
state: Chiba
city: Kisarazu
country: Japan
state: Chiba
city: Yotsukaido
country: Japan
state: Chiba
city: Imabari
country: Japan
state: Ehime
city: Matsuyama
country: Japan
state: Ehime
city: Niihama
country: Japan
state: Ehime
city: Chikushino
country: Japan
state: Fukuoka
city: Kasuga
country: Japan
state: Fukuoka
city: Kasuya-gun
country: Japan
state: Fukuoka
city: Kitakyushu
country: Japan
state: Fukuoka
city: Munakata
country: Japan
state: Fukuoka
city: Tajimi
country: Japan
state: Gifu
city: Takasaki
country: Japan
state: Gunma
city: Fukuyama
country: Japan
state: Hiroshima
city: Chitose
country: Japan
state: Hokkaido
city: Himeji
country: Japan
state: Hyogo
city: Takarazuka
country: Japan
state: Hyogo
city: Mito
country: Japan
state: Ibaragi
city: Sakai
country: Japan
state: Ibaragi
city: Fujisawa
country: Japan
state: Kanagawa
city: Kamakura
country: Japan
state: Kanagawa
city: Kawasaki
country: Japan
state: Kanagawa
city: Yokohama
country: Japan
state: Kanagawa
city: Sendai
country: Japan
state: Miyagi
city: Nakano
country: Japan
state: Nagano
city: Ueda
country: Japan
state: Nagano
city: Kasaoka
country: Japan
state: Okayama
city: Setouchi
country: Japan
state: Okayama
city: Fukaya
country: Japan
state: Saitama
city: Kumagaya
country: Japan
state: Saitama
city: Hamamatsu
country: Japan
state: Shizuoka
city: Yoshinogawa
country: Japan
state: Tokushima
city: Hachioji
country: Japan
state: Tokyo
city: Itabashi-ku
country: Japan
state: Tokyo
city: Kunitachi
country: Japan
state: Tokyo
city: Uozu
country: Japan
state: Toyama
city: Shimonoseki
country: Japan
state: Yamaguchi
city: Ube
country: Japan
state: Yamaguchi
city: Akita
country: Japan
city: Kumamoto
country: Japan
city: Nagano
country: Japan
city: Niigata
country: Japan
city: Osaka
country: Japan
city: Yamagata
country: Japan
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: