KJ-TFC-004 Drug-drug Interaction Study

A Randomized, Open-label, 2-period, Parallel Group, Multiple-dose Study to Evaluate the Drug-drugs Interaction Between Dorzolamide and Brimonidine in Healthy Korean Male Volunteers

To assess the pharmacokinetic Interaction between Dorzolamide and Brimonidine in healthy male subjects.

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Glaucoma; Eye Diseases
• Intervention / Treatment: Drug: [A]; Drug: [A]+[B](1); Drug: [B]; Drug: [A]+[B](2)

Detailed Description

Clinical trial to evaluate the influence of drug and drug-drug interactions of Brimonidine and Dorzolamide co-administration on the pharmacokinetics of Brimonidine and pharmacokinetics of Dorzolamide in healthy volunteers

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Clinical Trial Center, Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male adults aged between 19 and 50 during screening period
• BMI more than 18kg / m2 and less than 30kg / m2 and weight more than 55kg
• Signed the informed consent form prior to study participation.

Exclusion Criteria:

• Presence of medical history or a concurrent disease that may interfere with treatment and safety assessment or completion of this clinical study, including clinically significant disorders in kidney, liver, cardiovascular system, respiratory system, endocrine system, or neuropsychiatric system.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [A]→[A]+[B]; Period 1 : At each dosing of Treatment A eye drops is administered for 8days Period 2 : At each dosing of Treatment A + Treatment B eye drops is administered for 92days	Drug: [A]; One eye drop(about 40ul) / Day1 ~ Day8 / BID; Other Names: Brimonidine , Timolol; Drug: [A]+[B](1); One eye drop(about 40ul) / Day9 ~ Day100 / BID; Other Names: Brimonidine , Timolol , Dorzolamide
Experimental: [B]→[A]+[B]; Period 1 : At each dosing of Treatment B eye drops is administered for 92days Period 2 : At each dosing of Treatment A + Treatment B eye drops is administered for 8days	Drug: [B]; One eye drop(about 40ul) / Day1 ~ Day92 / BID; Other Names: Dorzolamide; Drug: [A]+[B](2); One eye drop(about 40ul) / Day93 ~ Day100 / BID; Other Names: Brimonidine , Timolol , Dorzolamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of Brimonidine and Dorzolamide	Group 1 Brimonidine Period 1 : 1d 0h,7d 0h,7d 12h,8d 0h(pre-dose), 8d 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12 h post-dose (Total 15 Point) Period 2 : 9d 0h,23d 0h,37d 0h,51d 0h,65d 0h,79d 0h,93d 0h,99d 0h,99d 12h, 100d 0h(pre-dose),100d 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12 h post-dose (Total 21Point) Dorzolamide Period 2 : 9d 0h,23d 0h,37d 0h,51d 0h,65d 0h,79d 0h,93d 0h,99d 0h,99d 12h,100d 0h (pre-dose), 100d 0.25,0.5,0.75,1,1.5,2,2.5,3,4,8,12 h post-dose (Total 21Point) Group 2 Brimonidine Period 2 : 93d 0h,99d 0h,99d 12h,100d 0h(pre-dose),100d 0.25, 0.5, 0.75, 1, 1.5,2,2.5,3,4,8,12h post-dose (Total 15Point) Dorzolamide Period 1 : 1d 0h, 15d 0h, 29d 0h, 43d 0h, 57d 0h, 71d 0h, 85d 0h, 91d 0h, 91d 12h, 92d 0h (pre-dose), 92d 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12 h post-dose (Total 21Point) Period 2 : 93d 0h, 99d 0h, 99d 12h, 100d 0h (pre-dose), 100d 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12 h post-dose (Total 15Point)	pre- and post dose of Brimonidine and Dorzolamide administration]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough concentration of Dorzolamide and N-Desethyl-Dorzloamide	Group 1 Brimonidine Period 1 : 1d 0h,7d 0h,7d 12h 8d 0h (pre-dose),8d 0.25,0.5,0.75,1,1.5,2,2.5,3, 4,8,12 h post-dose (Total 15Point) Period 2 : 9d 0h,23d 0h,37d 0h,51d 0h,65d 0h,79d 0h,93d 0h,99d 0h,99d 12h,100d 0h (pre-dose),100d 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12h post-dose (Total 21Point) Dorzolamide Period 2 : 9d 0h,23d 0h,37d 0h,51d 0h,65d 0h,79d 0h,93d 0h,99d 0h,99d 12h,100d 0h (pre-dose), 100d 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12h post-dose (Total 21Point) Group 2 Brimonidine Period 2 : 93d 0h,99d 0h,99d 12h,100d 0h (pre-dose),100d 0.25, 0.5, 0.75, 1, 1.5,2,2.5,3,4,8,12h post-dose (Total 15Point) Dorzolamide Period 1 : 1d 0h,15d 0h,29d 0h,43d 0h,57d 0h,71d 0h,85d 0h,91d 0h, 91d 12h,92d 0h(pre-dose), 92d 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12h post-dose (Total 21Point) Period 1 : 93d 0h,99d 0h,99d 12h,100d 0h (pre-dose), 100d 0.25, 0.5, 0.75, 1, 1.5,2,2.5,3,4,8,12h post-dose (Total 15Point)	pre- and post dose of Dorzolamide and Dorzloamide administration]

Collaborators and Investigators

• Sponsor: Kukje Pharma
• Investigators: Principal Investigator: Kyung-sang Yu, Ph.d., M.B.A, Clinical Trial Center, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: November 12, 2016
• First Submitted That Met QC Criteria: November 15, 2016
• First Posted (Estimate): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): April 11, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ocular Hypertension; Eye Diseases; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Carbonic Anhydrase Inhibitors; Timolol; Brimonidine Tartrate; Dorzolamide
• Other Study ID Numbers: KJ-TFC-004

Plan for Individual participant data (IPD)

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