A Dose-escalating Clinical Trial With KH176

Study Overview
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Brief Summary
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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

Official Title
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A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176

Conditions
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MELAS, LHON, Leigh Syndrome, Mitochondrial Disease, Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation

Intervention / Treatment
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* Drug: KH176
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Escalating<br>2 alternating groups receiving escalating single doses of active/placebo | Drug: KH176<br> <br> Drug: placebo<br> <br> |
| Experimental: Multiple Escalating<br>3 multiple escalating groups, receiving active/placebo | Drug: KH176<br> <br> Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF) | 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. | Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up | 
| Pharmacodynamics of KH176 | Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group | Day 1, day 7 | 
| Relationship to Study Drug and Severity of Treatment-emergent Adverse Events |  | 4 months | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group) |  | 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 |  | 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 | 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. | Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD | 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. | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD | 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. | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD | 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. | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) | 
| MAD: Change From Baseline in ECG Results by Time Point: QTcF | 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. | Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group | 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 | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group | 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. | Baseline (pre-dose Day 1), 24h, FU (7 days post-dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group | 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. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group | 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 | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group | 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. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group | 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. | Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group | 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. | Baseline, Day 3, Day 8, FU (one week after last dosing) | 
| Phospholipidosis | 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 | Day 1, Day 7 | 
| MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB) | 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. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up | 
| MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval) | 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. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up | 
| 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) | 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. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up | 
| MAD: Change From Baseline in ECG Results by Time Point: QT Interval | 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. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up | 
| SAD: Change From Baseline in ECG Results by Time Point: PQ Interval | 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. | Pre-dose, Day 1, Day 7 | 
| SAD: Change From Baseline in ECG Results by Time Point: QRS Interval | 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. | Pre-dose, Day 1, Day 7 | 
| SAD: Change From Baseline in ECG Results by Time Point: QT Interval | 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. | Pre-dose, Day 1, Day 7 | 
| SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval | 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. | Pre-dose, Day1, Day 7 | 
| Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Terminal Elimination Half-life (T1/2) of KH183: SAD | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Maximum Concentration (Cmax) of KH176: SAD Group | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group | 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. | 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 | 
| Maximum Concentration (Cmax) of KH176: MAD | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | 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 | 
| Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | 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 | 
| Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group | 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. | 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 | 
| Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group | 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. | 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 | 
| Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group | 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. | 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 | 
| Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group | 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. | pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group: | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | 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 | 
| Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | 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 | 
| Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD | 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. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose | 
| KH176: Percentage of Administered Dose Excreted in Urine: SAD | 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. | 24 hours post-dose | 
| KH183: Percentage of Administered Dose Excreted in Urine: SAD | 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. | 24 hours post-dose | 
| KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD | 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. | 24 hours post-dose | 
| KH176: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Day 7 post dose | 
| KH183: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Post dose Day 7 | 
| KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Day 7 Post dose |