The Practical Evidence of Antidiabetic Combination Therapy NCT02231021

Clinical Trial Details — Status: Completed

Administrative data
NCT number	NCT02231021
Other study ID #	ALO-IIT-012
Secondary ID
Status	Completed
Phase	Phase 4
First received
Last updated
Start date	September 2014
Est. completion date	January 28, 2019

Study information
Verified date	February 2019
Source	The Catholic University of Korea
Contact	n/a
Is FDA regulated	No
Health authority
Study type	Interventional

Clinical Trial Summary

This study evaluate the efficacy and safety of alogliptin and pioglitazone combination therapy in comparison with either alogliptin or pioglitazone on glucose control in the metformin-treated type 2 diabetic patients in Korea.

Description:

Pathophysiology of type 2 diabetes is known as insulin resistance and progressive beta cell dysfunction.

Combination therapy with biguanides, glucagon-like peptide-1(GLP-1) agonists or dipeptidyl peptidase-4 inhibitor(DPP4I) and thiazolidinediones(TZD) seems reasonable theoretically, for their effects on different pathophysiologic defects.

Current treatment guidelines recommend a stepwise approach starting with lifestyle modification or lifestyle modification + metformin monotherapy, with recent focusing on patient individualization.

In Korea, Korean Diabetes Association also recommends stepwise approach and at the same time, emphasizes on the initial aggressive treatment including oral combination or insulin therapy according to HbA1c level to achieve target goal <6.5%.

Guide to the efficacy, timing, options of combination therapy is not clearly defined due to lack of sufficient evidences yet.

There is no clear report to demonstrate the clinical benefit of initial TZD and DPP4I combination therapy in the Korean.

Thus it is reasonable to study the effect of combination therapy in the patients with sub-optimal glucose control with metformin therapy only, comparing various combination options metformin with DPP4I only, TZD only, or both.

The hypothesis of this study is that combination therapy of alogliptin and pioglitazone added on the metformin has superior effect on HbA1c reduction than metformin and either alogliptin or pioglitazone in 6 month treatment.

Recruitment information / eligibility
Status	Completed
Enrollment	216
Est. completion date	January 28, 2019
Est. primary completion date	October 22, 2018
Accepts healthy volunteers	No
Gender	All
Age group	19 Years to 75 Years
Eligibility	Inclusion Criteria: - In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements - The subject or, when applicable, the subject'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 - The subjects diagnosed type 2 diabetes mellitus at least 6 months - Male and female and 19 to 75 years, inclusive - 7.0% =<HbA1c =<10.0% - 18.5 Kg/m2 =<Body Mass Index(BMI) =<45 kg/m2 - systolic/diastolic blood pressure =<160/100 at baseline - hemoglobin of at least 12 g/dL for men and at least 10 g/dL for women - A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from singing of informed consent throughout the duration of the study - Patient who receiving maximal tolerated dose of metformin at least 12 weeks without dose change (for metformin, >= 1,000 mg/day - fasting c-peptide greater than 0.78 ng/mL(0.26 nmol/L) at baseline Exclusion Criteria: - The patient has received investigational compound(alogliptin or pioglitazone) within 180 days prior to baseline - Patient who currently taking or need to take andy medicine which may exert a significant influence on blood glucose control except metformin. - Severe renal disease : estimated glomerular filtration rate <50 mL/min - Severe liver disease or AST, ALT >= 2.5 upper limit of normal - Cardiac status : New York Heart Association III ~ IV - Hypopituitarism or adrenal insufficiency - Patient who has a history of major surgery, Severe infections, Severe traumas within 6 months - Patients who has diagnosed malignancy within 5yrs , - Patients with active bladder cancer - Patient with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption - Patient who has a history of hypersensitivity to Alogliptin, Pioglitazone or their ingredients - Pregnant or lactating woman - Patient who has history of excessive alcohol abuse - Subject who is involved in other clinical trial within 90 days prior to initiation of this study. - Subject who the investigator deems inappropriate to participate in this study

Study Design

Related Conditions & MeSH terms

Intervention

Drug:
• alogliptin
alogliptin 25 mg add-on background medication metformin
• Pioglitazone
pioglitazone 30 mg add-on background medication metformin
• alogliptin + pioglitazone
alogliptin 25 mg and pioglitazone 30 mg add-on background medication metformin

Locations
Country	Name	City	State
Korea, Republic of	Seoul St Mary's Hospital, The Catholic University of Korea	Seoul

Sponsors *(2)*
Lead Sponsor	Collaborator
Kun-Ho Yoon	Takeda

Country where clinical trial is conducted

Korea, Republic of,

Outcome
Type	Measure	Description	Time frame
Primary	Change in glycohemoglobin(HbA1c) from baseline		baseline, 24 weeks
Secondary	Proportion of subjects achieving HbA1c < 7.0%		24 week
Secondary	Proportion of subjects achieving HbA1c <6.5%		24 week
Secondary	Changes in glycated albumin(GA) from baseline		baseline, 24 weeks
Secondary	Change in GA/HbA1c ratio from baseline		baseline, 24 weeks
Secondary	Change in fasting blood sugar from baseline		baseline, 24 weeks
Secondary	Incidence of hyperglycemic rescue	at Week 12, HbA1c >9.0%	12 week
Secondary	Change in HbA1c from baseline		12 week
Secondary	Change in total cholesterol from baseline		baseline, 24 weeks
Secondary	Change in triglycerides from baseline		baseline, 24 weeks
Secondary	Change in LDL-cholesterol from baseline		baseline, 24 weeks
Secondary	Change in HDL-cholesterol from baseline		baseline, 24 weeks
Secondary	Changes in glycated albumin(GA) from baseline		baseline, 12 weeks
Secondary	Change in GA/HbA1c ratio from baseline		baseline, 12 weeks
Secondary	Change in fasting blood sugar from baseline		baseline, 12 weeks
Secondary	Change in total cholesterol from baseline		baseline, 12 weeks
Secondary	Change in triglycerides from baseline		baseline, 12 weeks
Secondary	Change in LDL-cholesterol from baseline		baseline, 12 weeks
Secondary	Change in HDL-cholesterol from baseline		baseline, 12 weeks
Secondary	Change in Homeostasis Model Assessment-Insulin resistance(HOMA-IR) from baseline	a marker of insulin resistance	baseline, 24 weeks
Secondary	Change in Homeostasis Model Assessment - beta cell (HOMA-beta) from baseline	a marker of beta cell function	baseline, 24 weeks
Secondary	Change in highly sensitive C reactive protein(hs-CRP) from baseline	a marker of inflammation	baseline, 24 weeks
Secondary	Change in Plasmonogen activator inhibitor-1(PAI-1) from baseline		baseline, 24 weeks
Secondary	Change in B-type natriuretic pepetide(BNP) from baseline		baseline, 24 weeks
Secondary	event rate of hypoglycemia	A number of total event of hypoglycemia defined as blood glucose <70mg/dL or subjective symptom of typical hypoglycemia	upto 24 weeks
Secondary	No of subject with adverse event of special interest	The event of special interest include heart failure cardiovascular effect other than heart failure edema weight gain urinary bladder tumor macular edema fracture of bone pancreatitis	upto 24 weeks
Secondary	The number of serious adverse events		upto 24 weeks
Secondary	The number of subject with hypersensitivity to study drugs		upto 24 weeks
Secondary	The number of subject with any abnormality of laboratory evaluation	Complete Blood count BUN, Creatinine, AST, ALT, Calcium, Phosphorous, Sodium, Potassium, Total Protein, Albumin, Total Bilirubin, Gamma-glutamyl transferase, Alkaline phosphatase, Creatinine Kinase, amylase, lipase Urine analysis including microscopic examination	12 week
Secondary	The number of subject with any abnormality of laboratory evaluation	Complete Blood count Blood urea nigrogen, Creatinine, Aspartate aminotransferase, Alanine Aminotransferase, Calcium, Phosphorous, Sodium, Potassium, Total Protein, Albumin, Total Bilirubin, Gamma-glutamyl transferase, Alkaline phosphatase, Creatinine Kinase, amylase, lipase Urine analysis including microscopic examination	24 week
Secondary	The number of subject with any change of findings in Chest X-ray from baseline		24 week
Secondary	The number of subject with any change of findings in electrocardiogram from baseline		24 week

See also
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The Practical Evidence of Antidiabetic Combination Therapy in Korea

Clinical Trial Details — Status: Completed

Administrative data

Study information

Clinical Trial Summary

Description:

Recruitment information / eligibility

Study Design

Related Conditions & MeSH terms

Intervention

Locations

Sponsors (2)

Country where clinical trial is conducted

Outcome