Clinical trial NCT03499704: A Study to Evaluate the Effect of add-on Pioglitazone or Dapagliflozin in Participants With Type 2 Diabetes Mellitus Inadequately Controlled by DPP-4 Inhibitor and Metformin Therapy
Official title: A Multicenter, Randomized, Open-label, Two-arm, Phase 4 Study to Evaluate the Effect of Add-on Pioglitazone or Dapagliflozin in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled by Dipeptidyl Peptidase-4 Inhibitor and Metformin Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Drug therapy
Lead sponsor: Celltrion Pharm, Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-17
Enrollment: 133
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
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 assess the pioglitazone plus alogliptin plus metformin is non-inferior to dapagliflozin plus alogliptin plus metformin on glycosylated haemoglobin (HbA1c) change from baseline at Week 26.

Detailed description: The drug being tested in this study is Alogliptin Benzoate and Pioglitazone Hydrochloride FDC. This study will assess the efficacy of pioglitazone or dapagliflozin in participants with type 2 diabetes mellitus.

The study will enroll approximately 156 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups.

* Pioglitazone 15 mg + Alogliptin 25 mg + Metformin \>=500 mg
* Dapagliflozin 10 mg + Alogliptin 25 mg + Metformin \>=500 mg

Based on investigators opinion at Week 12, if participant has HbA1c \>=7.5%, dose of pioglitazone can be titrated up to 30 mg.

This multi-center trial will be conducted in Republic of Korea. The overall time to participate in this study is up to 36 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 14 days after their last dose of drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. The subject is a regular outpatient with an has a historical diagnosis of type 2 diabetes.
2. The subject has metabolic syndrome as jointly defined by the International Diabetes Federation (IDF); National Heart, Lung, and Blood Institute (NHLBI) / American Heart Association (AHA); and International Association for the Study of Obesity (IASO). If any 3 of the following 5 risk factors are present, metabolic syndrome can be considered:

   * High waist circumference: male ≥ 90 cm, female ≥ 85 cm.
   * High TGs (drug treatment for high TGs is an alternate indicator): ≥ 150 mg/dL (1.7 mmol/L).
   * Low HDL-C (drug treatment for low HDL-C is an alternate indicator): \< 40 mg/dL(1.0 mmol/L) in males, \< 50 mg/dL (1.3 mmol/L) in females.
   * High blood pressure (antihypertensive drug treatment in a subject with a history of hypertension is an alternate indicator): Systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg.
   * High fasting glucose (drug treatment of high glucose is an alternate indicator): ≥ 100 mg/dL.
3. The subject has been receiving a stable dose of DPP-4 inhibitor + metformin therapy with diet and exercise for ≥ 3 months prior to Randomization.
4. The subject has a HbA1c value between 7.0 and 11% inclusively within 28 days of Randomization via central laboratory test or after run-in period for 4 weeks via central laboratory test.

Exclusion Criteria:

1. The subject has type 1 diabetes, diabetic ketoacidosis, diabetic coma or diabetic precoma.
2. The subject has an active bladder cancer or a history of bladder cancer.
3. The use of any medications ie, oral or systemically injected glucocorticoids (including intra-articular injection), weight-loss drugs, insulin or other anti-diabetic drugs except DPP-4 inhibitor and metformin, within 3 months prior to randomization. Strong Cytochrome P450 2C8 (CYP2C8) inhibitors (eg, gemfibrozil, montelukast, quercetin, phenelzine) and CYP2C8 inducers (eg, rifampin) that in the opinion of the Investigator or Sponsor require treatment contraindicated during the study. The diuretics, angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) -inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) are to be used per product label with close monitoring under Investigator's supervision.
4. Has genetic problems such as galactose intolerance, Lapp lactose dehydrogenase deficiency or glucose-galactose uptake disorder, etc.
5. Has a history of alcohol abuse within 2 years prior to randomization.

Primary outcomes:
measure: Mean Change from Baseline in HbA1c at Week 26
timeFrame: Baseline and Week 26
Secondary outcomes:
measure: Mean Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 26
timeFrame: Baseline and Week 26
measure: Mean Change from Baseline in Serum Lipids at Week 26
timeFrame: Baseline and Week 26
measure: Number of Participants who Achieved an HbA1c Goal Target of Less than (<) 6.5 Percent (%) at Week 26
timeFrame: Week 26
Other outcomes:
Locations:
city: Bucheon-si
country: Korea, Republic of
facility: The Catholic University of Korea, Bucheon, St. Marys Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, ST. Vincents Hospital
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: YeungNam University Hospital
city: Daejeon
country: Korea, Republic of
facility: Daejeon Eulji Medical Center, Eulji University
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
Study officials:
affiliation: Celltrionpharm Inc.
name: Medical Team
role: STUDY_DIRECTOR
References: