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A Dose-escalating Clinical Trial With KH176

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02544217
Recruitment Status : Completed
First Posted : September 9, 2015
Results First Posted : November 12, 2020
Last Update Posted : October 18, 2021
Sponsor:
Collaborator:
Drug Research Unit Ghent, Belgium
Information provided by (Responsible Party):
Khondrion BV

Tracking Information
First Submitted Date  ICMJE April 19, 2015
First Posted Date  ICMJE September 9, 2015
Results First Submitted Date  ICMJE June 23, 2020
Results First Posted Date  ICMJE November 12, 2020
Last Update Posted Date October 18, 2021
Study Start Date  ICMJE May 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2020)
  • SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF) [ Time Frame: Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
  • Pharmacodynamics of KH176 [ Time Frame: Day 1, day 7 ]
    Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group
  • Relationship to Study Drug and Severity of Treatment-emergent Adverse Events [ Time Frame: 4 months ]
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group) [ Time Frame: Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing) ]
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing) ]
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing) ]
    Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD [ Time Frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD [ Time Frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) ]
    Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD [ Time Frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • MAD: Change From Baseline in ECG Results by Time Point: QTcF [ Time Frame: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h, FU (7 days post-dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group [ Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group [ Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group [ Time Frame: Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group [ Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing) ]
    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
  • Phospholipidosis [ Time Frame: Day 1, Day 7 ]
    Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD
  • MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB) [ Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
  • MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval) [ Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.
  • 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) [ Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
  • MAD: Change From Baseline in ECG Results by Time Point: QT Interval [ Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
  • SAD: Change From Baseline in ECG Results by Time Point: PQ Interval [ Time Frame: Pre-dose, Day 1, Day 7 ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
  • SAD: Change From Baseline in ECG Results by Time Point: QRS Interval [ Time Frame: Pre-dose, Day 1, Day 7 ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
  • SAD: Change From Baseline in ECG Results by Time Point: QT Interval [ Time Frame: Pre-dose, Day 1, Day 7 ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
  • SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval [ Time Frame: Pre-dose, Day1, Day 7 ]
    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
  • Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • Terminal Elimination Half-life (T1/2) of KH183: SAD [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
  • Maximum Concentration (Cmax) of KH176: SAD Group [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
  • Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group [ Time Frame: 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 ]
    Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.
  • Maximum Concentration (Cmax) of KH176: MAD [ Time Frame: 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 ]
    Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
  • Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group [ Time Frame: 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 ]
    Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
  • Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group [ Time Frame: 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 ]
    Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.
  • Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group [ Time Frame: 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 ]
    Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.
  • Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group [ Time Frame: 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 ]
    Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.
  • Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
  • Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group [ Time Frame: pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group: [ Time Frame: 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 ]
    Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
  • Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group [ Time Frame: 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 ]
    Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
  • Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
  • Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD [ Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose ]
    Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
  • KH176: Percentage of Administered Dose Excreted in Urine: SAD [ Time Frame: 24 hours post-dose ]
    Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • KH183: Percentage of Administered Dose Excreted in Urine: SAD [ Time Frame: 24 hours post-dose ]
    Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD [ Time Frame: 24 hours post-dose ]
    Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
  • KH176: Percentage of Administered Dose Excreted in Urine: MAD [ Time Frame: Day 7 post dose ]
    Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
  • KH183: Percentage of Administered Dose Excreted in Urine: MAD [ Time Frame: Post dose Day 7 ]
    Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
  • KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD [ Time Frame: Day 7 Post dose ]
    Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Original Primary Outcome Measures  ICMJE
 (submitted: September 4, 2015)
  • Safety and tolerability (assessment of adverse events, routine clinical laboratory, vital signs, ECG, physical exam) [ Time Frame: 4 months ]
    assessment of adverse events, routine clinical laboratory, vital signs, ECG, physical exam
  • Pharmacokinetics of KH176 [ Time Frame: 7 days ]
    assessment of time to reach peak plasma concentration
  • Pharmacokinetics of KH176 [ Time Frame: 7 days ]
    assessment of peak plasma concentration
  • Pharmacokinetics of KH176 [ Time Frame: 7 days ]
    assessment of the area under the plasma concentration versus time curve (AUC)
  • Pharmacokinetics of KH176 [ Time Frame: 7 days ]
    assessment of half life
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2015)
Pharmacodynamics of KH176 [ Time Frame: 7 days ]
change from baseline in biochemistry related to OXPHOS (glutathione, lactate)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose-escalating Clinical Trial With KH176
Official Title  ICMJE A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • MELAS
  • LHON
  • Leigh Syndrome
  • Mitochondrial Disease
  • Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation
Intervention  ICMJE
  • Drug: KH176
  • Drug: placebo
Study Arms  ICMJE
  • Experimental: Single Escalating
    2 alternating groups receiving escalating single doses of active/placebo
    Interventions:
    • Drug: KH176
    • Drug: placebo
  • Experimental: Multiple Escalating
    3 multiple escalating groups, receiving active/placebo
    Interventions:
    • Drug: KH176
    • Drug: placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 20, 2020)
32
Original Estimated Enrollment  ICMJE
 (submitted: September 4, 2015)
30
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02544217
Other Study ID Numbers  ICMJE KH176-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Khondrion BV
Study Sponsor  ICMJE Khondrion BV
Collaborators  ICMJE Drug Research Unit Ghent, Belgium
Investigators  ICMJE Not Provided
PRS Account Khondrion BV
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP