Clinical trial NCT02544217: A Dose-escalating Clinical Trial With KH176
Official title: A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: MELAS
LHON
Leigh Syndrome
Mitochondrial Disease
Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation
Lead sponsor: Khondrion BV
Sponsor class: INDUSTRY
Collaborators: name: University Ghent
First posted: 2015-09-09
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Mitochondrial Diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), Leigh's Disease and Leber's Hereditary Optic Neuropathy (LHON). KH176 is a potent intracellular redox modulating agent targeting the reactive oxygen species which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. After demonstrating a favourable safety profile in the pre-clinical testing, the safety, tolerability and pharmacokinetic and pharmacodynamic characteristics of the compound will now be evaluated in healthy male subjects in this trial


Eligibility criteria: Inclusion Criteria:

* Healthy as assessed by medical history, physical examination, Vital Signs, Clinical Laboratory, ECG

Exclusion Criteria:

* Allergies,
* Concomitant medication,
* concomitant disease,
* relevant surgery,
* recent blood donation

Primary outcomes:
measure: SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
timeFrame: Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up
measure: Pharmacodynamics of KH176
timeFrame: Day 1, day 7
measure: Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
timeFrame: 4 months
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)
timeFrame: Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group
timeFrame: Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD
timeFrame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD
timeFrame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD
timeFrame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
measure: MAD: Change From Baseline in ECG Results by Time Point: QTcF
timeFrame: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h, FU (7 days post-dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
timeFrame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group
timeFrame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
timeFrame: Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
timeFrame: Baseline, Day 3, Day 8, FU (one week after last dosing)
measure: Phospholipidosis
timeFrame: Day 1, Day 7
measure: MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
timeFrame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
measure: MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
timeFrame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
measure: MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
timeFrame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
measure: MAD: Change From Baseline in ECG Results by Time Point: QT Interval
timeFrame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
measure: SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
timeFrame: Pre-dose, Day 1, Day 7
measure: SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
timeFrame: Pre-dose, Day 1, Day 7
measure: SAD: Change From Baseline in ECG Results by Time Point: QT Interval
timeFrame: Pre-dose, Day 1, Day 7
measure: SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
timeFrame: Pre-dose, Day1, Day 7
measure: Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Terminal Elimination Half-life (T1/2) of KH183: SAD
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Maximum Concentration (Cmax) of KH176: SAD Group
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group
timeFrame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Maximum Concentration (Cmax) of KH176: MAD
timeFrame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group
timeFrame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group
timeFrame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group
timeFrame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group
timeFrame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group
timeFrame: pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:
timeFrame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group
timeFrame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
measure: Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD
timeFrame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
measure: KH176: Percentage of Administered Dose Excreted in Urine: SAD
timeFrame: 24 hours post-dose
measure: KH183: Percentage of Administered Dose Excreted in Urine: SAD
timeFrame: 24 hours post-dose
measure: KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD
timeFrame: 24 hours post-dose
measure: KH176: Percentage of Administered Dose Excreted in Urine: MAD
timeFrame: Day 7 post dose
measure: KH183: Percentage of Administered Dose Excreted in Urine: MAD
timeFrame: Post dose Day 7
measure: KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD
timeFrame: Day 7 Post dose
Secondary outcomes:
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Drug Research Unit Ghent
Study officials:
References:
citation: Koene S, Spaans E, Van Bortel L, Van Lancker G, Delafontaine B, Badilini F, Beyrath J, Smeitink J. KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers. Orphanet J Rare Dis. 2017 Oct 16;12(1):163. doi: 10.1186/s13023-017-0715-0.