Condition category
Genetic Diseases
Date applied
23/06/2017
Date assigned
27/06/2017
Last edited
12/07/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Mitochondrial diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a new drug currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), Leigh's Disease and LHON (Leber's Hereditary Optic Neuropathy). Having been found to be safe in pre-clinical tests, the aim of this study is to assess the safety, tolerability (side effects) and pharmacokinetic and pharmacodynamic characteristics of KH176 in healthy male volunteers. Pharmacodynamics is the study of how a drug affects the body, whereas pharmacokinetics is the study of how the body affects the drug.

Who can participate?
Healthy adult male volunteers

What does the study involve?
The study involves two parts. For the first part, participants are randomly allocated to receive either KH176 (at six different doses) or placebo (dummy drug), with one week in between each dose. Pharmacokinetic, pharmacodynamic and safety tests take place before dosing and on the day of dosing up to 24 hours after dosing and at follow-up one week later. For the second part participants are randomly allocated to receive either KH176 (at three different doses) or placebo twice a day for 7 days. Pharmacokinetic, pharmacodynamic and safety tests take place before dosing and at multiple days after dosing, and at follow-up one week after the last dose is given.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Drug Research Unit Genth (Belgium)

When is the study starting and how long is it expected to run for?
April 2015 to October 2015

Who is funding the study?
Khondrion (Netherlands)

Who is the main contact?
Dr Edwin Spaans

Trial website

Contact information

Type

Public

Primary contact

Dr Edwin Spaans

ORCID ID

Contact details

Philips van Leydenlaan 15
Nijmegen
6500 HB Nijmegen
Netherlands

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT02544217

Protocol/serial number

KH176-101

Study information

Scientific title

A Phase I, randomized, double-blind, placebo-controlled, dose-escalating clinical trial with KH176

Acronym

Study hypothesis

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 Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes (MELAS), 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.

Ethics approval

Comité voor Medische Ethiek (Committee for Medical Ethics), 05/06/2015, ref: 2015/0508

Study design

Randomized crossover double-blind placebo-controlled single-center trial

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Mitochondrial disease

Intervention

For the single-ascending dose (SAD) part, a partial alternating crossover design was applied. The effects of 6 single orally administered ascending doses of KH176 of 10, 30, 100, 300, 800 and 2000 mg or placebo were investigated alternately dosed to two groups of 6 healthy male subjects. For each dose, 4 subjects received active treatment and 2 subjects received placebo, with one week in between dosing (thus resulting in a 2-week washout period for each subject in an alternating cross-over design). Pharmacokinetic, pharmacodynamic and safety evaluations took place prior to dosing and on the day of dosing up to 24 hours post dosing and at follow-up one week later.

For the multiple-ascending dose (MAD) part a sequential group design was applied. In the MAD part 3 multiple ascending doses of KH176 of 100, 200 and 400 mg b.i.d. were administered for 7 days to 3 sequential groups of 6 healthy male subjects each. For each dose 4 subjects received active treatment and 2 subjects received placebo. In the MAD part, pharmacokinetic, pharmacodynamic and safety evaluations took place prior to dosing and at multiple days post-dosing, and at follow-up one week after the last dose was administered.

Intervention type

Drug

Phase

Phase I

Drug names

KH176

Primary outcome measures

1. Pharmacokinetic parameters (peak plasma concentration, time to reach peak plasma concentration, area under the plasma concentration versus time curve [AUC], half life), non-compartmentally derived from measurement of plasma concentrations of KH176 and its metabolite at pre-dose and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose in the SAD part and at 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 in the MAD part
2. Safety and tolerability:
2.1. In the SAD part vital signs recorded pre-dose and 1, 2, 4, 6, 8, 12 and 24 hours post-dosing. In the MAD part vital signs recorded pre-dose on Day 1, and 1, 2, 4, 6, 8, 12 hours post dosing on Day 1, pre-dose on Day 2, 3, 4, 5, 6 and 7 and 1, 2, 4, 6 and 12 hours post dosing on Day 7
2.2. ECG recordings obtained at pre-dose (triplicate recording) and 1, 2, 4, 6, 8, 12 and 24 hours post-dosing in the SAD part, and at pre-dose (triplicate recording) and 1, 2, 4, 6, 8, 12 hours post dosing on Day 1 and pre-dose on Day 2, 3, 4, 5, 6 and 7 and 1, 2, 4, 6, 8 and 12 hours post dosing on Day 7
2.3. Adverse events evaluated continuously for the entire dosing period

Secondary outcome measures

Pharmacodynamic parameters of KH176: changes in biochemistry related to OXPHOS (glutathione, lactate) from baseline to Day 7

Overall trial start date

01/04/2015

Overall trial end date

10/10/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy as assessed by medical history, physical examination, vital signs, clinical laboratory, ECG
2. Adult males

Participant type

Healthy volunteer

Age group

Adult

Gender

Male

Target number of participants

30

Participant exclusion criteria

1. Allergies
2. Concomitant medication
3. Concomitant disease
4. Relevant surgery
5. Recent blood donation

Recruitment start date

01/04/2015

Recruitment end date

30/04/2015

Locations

Countries of recruitment

Belgium

Trial participating centre

Drug Research Unit Genth
De Pintelaan 185
Gent
9000

Sponsor information

Organisation

Khondrion

Sponsor details

Philips van Leydenlaan 15
Nijmegen
6500 HB
Netherlands

Sponsor type

Industry

Website

www.khondrion.com

Funders

Funder type

Industry

Funder name

Khondrion

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available.

Intention to publish date

31/12/2017

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

12/07/2017: Internal edits.