Clinical Trial to Evaluate the Drug Drug Interaction of CKD-501 and D308

A Randomized, Open-label, Multiple Dose, 2-way Crossover Study to Evaluate the Drug Drug Interaction of CKD-501 and D308 in Healthy Volunteers

Phase 1 trial to evaluate the drug drug interaction of CKD-501 and D308

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type II
• Intervention / Treatment: Drug: D308, CKD-501

Detailed Description

A randomized, open-label, multiple dose, 2-way crossover study to evaluate the drug drug interaction of CKD-501 and D308 in healthy volunteers

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jeonju, Korea, Republic of
    • Chonbuk National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adult older than 19 years at the time of screening
2. BMI 17.5~30.5kg/m2 and body weight more than 55kg
3. Subject who has no chronic disease within last 3 years and no symptoms or pathological findings
4. Suitable subject who is determined to be suitable at the time of screening such as laboratory tests(hematology, blood chemistry, urinalysis, virus/bacteriological test, etc.), sign of vitality, electrocardiogram
5. Subject who signed the written consent of the Chonbuk National University Hospital IRB to participate in this study with full understanding of the purpose and contents of the examination prior to the clinical trial
6. Subject who has will and ability to participate in clinical trials

Exclusion Criteria:

1. Subject who has a history of clinical significant blood, kidney, endocrine, respiratory, gastrointestinal, urinary, cardiovascular, liver, psychiatric, neurological or allergic diseases(except for asymptomatic seasonal allergies not treated at the time of administration) or evidence(except for simple dental history such as dental calculus, impacted tooth, wisdom tooth, etc.)
2. Subject with a history of gastrointestinal disorders(esophageal achalasia or esophagus stenosis, Crohn's disease) or gastrointestinal surgery(except for simple appendicitis surgery or hernia surgery or tooth extraction surgery) that may affect the absorption

3. Clinical laboratory test results showing the following values

   * ALT or AST > 2 times upper limit of normal range

4. Subject who has a history of regular alcohol consumption exceeding 210g/week within 6months of screening (1 glass of beer(5%)=10g, 1 glass of soju(20%)=8g, 1 glass of wine(12%)=12g)
5. Those taking other clinical trial drugs or bioequivalence test drugs within 3months before the first administration of clinical trial drug
6. Subject who has a systolic blood pressure of less than 100mmHg or more than 140mmHg or diastolic blood pressure of less than 60mmHg or more than 90mmHg of screening
7. Subject who has significant alcohol abuse or drug abuse within a year of screening
8. Those taking medication known to significantly induce or inhibit drug metabolizing enzymes within 30days prior to the first administration of clinical trial medication
9. More than 20 smokers per day within six months of screening
10. Those taking prescription or non-prescription drugs within 10days before the first administration of clinical trial medication
11. Those who donated whole blood within 2 months or those who donated the components within 1 month before the first administration of the clinical trial drug
12. Subject who has risk of serious or chronic medical, mental, or laboratory examinations that may increase the risk due to the administration of medicines for clinical trials and may interfere with the interpretation of test results
13. Patients who are known to be hypersensitive to the drug or its components
14. Patients with severe heart failure or heart failure(New York Heart Association(NYHA) Class 3, 4 heart patients)
15. Patients with hepatic impairment
16. Patients with a glomerular filtration rate(eGFR) less than 60ml/min/1.73m2, patients with end stage renal disease or dialysis
17. Patients with diabetic ketoacidosis, diabetic coma and total coma, patients with type 1 diabetes
18. Before and after surgery, severe infectious patients, severe trauma patients
19. Subjects with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
20. Pregnant and lactating women
21. Subject who is judged by the investigator to be ineligible to participate in the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Group 1(Treatment A/Treatment B); Period 1: Treatment A (D308 1T)/day for 5days, QD, PO Period 2: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO	Drug: D308, CKD-501; D308; CKD-501: Lobeglitazone sulfate 0.5mg
Experimental: Part 1: Group 2(Treatment B/Treatment A); Period 1: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO Period 2: Treatment A (D308 1T)/day for 5days, QD, PO	Drug: D308, CKD-501; D308; CKD-501: Lobeglitazone sulfate 0.5mg
Experimental: Part 2: Group 1(Treatment C/Treatment B); Period 1: Treatment C (CKD-501 1T)/day for 5days, QD, PO Period 2: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO	Drug: D308, CKD-501; D308; CKD-501: Lobeglitazone sulfate 0.5mg
Experimental: Part 2: Group 2(Treatment B/Treatment C); Period 1: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO Period 2: Treatment C (CKD-501 1T)/day for 5days, QD, PO	Drug: D308, CKD-501; D308; CKD-501: Lobeglitazone sulfate 0.5mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part 1) AUCss,tau of D308	Area under the curve of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) Css,max of D308	Max Concentration of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) AUCss,tau of CKD-501	Area under the curve of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) Css,max of CKD-501	Max Concentration of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part 1) Css,min of D308	Min concentration of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) Css,av of D308	average concentration of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) Tss,max of D308	time of Max concentration of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) t1/2 of D308	half-life time of D308	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) CLss/F of D308	Apparent clearance of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) Vdss/F of D308	Apparent volume of distribution of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) Fluctuation[(Css,max-Css,min)/Css,av] of D308	Fluctuation concentration of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 1) Swing[(Css,max-Css,min)/Css,min] of D308	Swing concentration of D308 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) Css,min of CKD-501	Min concentration of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) Css,av of CKD-501	average concentration of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) Tss,max of CKD-501	time of Max concentration of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) t1/2 of CKD-501	half-life time of CKD-501	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) CLss/F of CKD-501	Apparent clearance of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) Vdss/F of CKD-501	Apparent volume of distribution of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) Fluctuation[(Css,max-Css,min)/Css,av] of CKD-501	Fluctuation concentration of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours
(Part 2) Swing[(Css,max-Css,min)/Css,min] of CKD-501	Swing concentration of CKD-501 at steady state	Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical

Publications and helpful links

General Publications

• Jang K, Jeon JY, Moon SJ, Kim MG. Evaluation of the Pharmacokinetic Interaction Between Lobeglitazone and Dapagliflozin at Steady State. Clin Ther. 2020 Feb;42(2):295-304. doi: 10.1016/j.clinthera.2020.01.003. Epub 2020 Jan 25.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2018
• Primary Completion (Actual): September 17, 2018
• Study Completion (Actual): November 13, 2018

Study Registration Dates

• First Submitted: July 8, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): November 19, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes Mellitus, Type II
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 19DDI18013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No