The purpose of the study is to investigate to what extent MIN-102 is tolerated.It will also be investigated how quickly and to what extent MIN-102 is absorbed and eliminated from the body (this is called pharmacokinetics). In addition, the effect of…
ID
Source
Brief title
Condition
- Metabolism disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A:
To evaluate the safety and tolerability of MIN-102 administered orally as a
single dose in healthy male volunteers.
Part B:
To evaluate the safety and tolerability of MIN-102 administered orally as a
multiple dose in healthy male volunteers.
Part C:
To evaluate the safety and tolerability of MIN-102 administered orally as a
multiple dose in healthy male volunteers.
Secondary outcome
Part A:
- To evaluate the PK parameters in plasma and urine of MIN-102 and M3 after a
single oral administration of MIN-102 in healthy male volunteers.
- To evaluate the food effect (FE) in the PK of MIN-102 and M3 after a single
oral administration of MIN-102 in healthy male volunteers.
- To evaluate the enantiomer proportionality of MIN-102 in plasma.
- To evaluate the adiponectin and fatty acid binding protein 4 (FABP4) levels
in plasma before and after a single dose of MIN-102
Part B:
- To evaluate the PK parameters in plasma and CSF of MIN-102 and M3 after
single and multiple oral administrations of MIN-102 in healthy male volunteers.
- To evaluate the levels in plasma and CSF of biomarkers (adiponectin, FABP4,
cytokines [interleukin 6 (IL-6), interleukin 1 receptor agonist (IL-1ra),
interleukin-8 (IL-8)] chemokines [monocyte chemotactic protein 1 (MCP-1), C-X-C
motif chemokine 10-Interferon gamma-induced protein 10 (CXCL10*IP10)], and
adhesion molecules [soluble intercellular adhesion molecules (sICAM) and
soluble vascular cellular adhesion molecule-1 (sVCAM1)]) after multiple oral
administrations of MIN-102.
Part C:
- To evaluate the PK parameters in plasma and cerebrospinal fluid (CSF) of
MIN-102 and M3 after single and multiple oral administrations of MIN-102 in
healthy male volunteers.
- To evaluate the levels of biomarkers (adiponectin, FABP4, CRP, cytokines
[IL-6, IL- 1ra, IL-8] chemokines [MCP-1, CXCL10*IP10], and adhesion molecules
[sICAM and sVCAM1]) in plasma and CSF after multiple oral administrations of
MIN-102.
Background summary
MIN-102 is a new investigational compound that may eventually be used for the
treatment of X-linked adrenoleukodystrophy (X-ALD). X-ALD is a relatively rare
inherited metabolic disorder affecting the metabolism of very long-chain fatty
acids (VLCFA). This results in high levels of VLCFA primarily in brain cells
and adrenocortical cells. These high levels of VLCFA cause damage to the
nervous system (degradation of myelin, an isolating layer around the axon of
nervous cells) and the steroid producing adrenocortical and testes cells.
MIN-102 interacts with a receptor regulating the fatty acid storage and glucose
metabolism. MIN-102 is a differentiated peroxisome proliferator-activated
receptor * (PPAR*) agonist. This is the first time that this study compound is
being given to humans.
MIN 102 is an active metabolite of the marketed drug Pioglitazone which is used
in the treatment of type 2 diabetes (T2D). Approximately 25% of Pioglitazone is
transferred to M4 (MIN-102) in the body.
Study objective
The purpose of the study is to investigate to what extent MIN-102 is tolerated.
It will also be investigated how quickly and to what extent MIN-102 is absorbed
and eliminated from the body (this is called pharmacokinetics). In addition,
the effect of MIN-102 on enzymes related to X-ALD will be investigated (this is
called pharmacodynamics).
Study design
Part A:
The study will consist of 4 periods during which the volunteer will stay in the
clinical research center in Groningen for 7 days (6 nights). The time interval
between the different periods is approximately 7 days.
Part B:
The study will consist of 1 period during which the volunteer will stay in the
clinical research center in Groningen for 15 days (14 nights).
Part C:
The study will consist of 1 period during which the volunteer will stay in the
clinical research center in Groningen for 15 days (14 nights).
Intervention
Part A:
The study will consist of 4 periods during which the volunteer will receive
MIN-102 or placebo once in each period. MIN-102 and placebo will be given as
oral suspension of 20 mL.
Part B:
The study will consist of 1 period during which the volunteer will receive
MIN-102 or placebo once daily for 8 days. MIN-102 and placebo will be given as
an oral suspension of 20 mL.
Part C:
The study will consist of 1 period during which the volunteer will receive
MIN-102 once daily for 8 days. MIN-102 will be given as an oral suspension of
not more than 20 mL. The dose levels used in Part C of the study are not known
yet: The dose for the first group of
Part B will be determined based on the results of Part A where 3 doses are
tested (planned doses 30, 60 and 120 mg). The dose level for the second group
of Part C will be determined based on the results of Part A of the study and
the results of the first groups of Part B and Part C.
Study burden and risks
All potential drugs cause adverse effects; the extent to which this occurs
differs. As MIN-102 will be administered to man for the first time in this
study, adverse effects of MIN-102 in man have not been reported to date.
However, MIN-102 has been studied in animals. The following adverse effects
were observed, only at the highest dose given, in animals: decreased
bodyweight, goose bumps, rough coat, and hunched posture. Excess saliva
production and abnormal blood values were also observed.
MIN-102 is a natural active metabolite of Pioglitazone, a drug that has been on
the market for several years and has been prescribed to many T2D patients. In
effect, many people have been exposed to the study compound, though in lower
doses. For Pioglitazone the most frequently described adverse effects in man
were: common (may affect up to 1 in 10 people): respiratory infection, abnormal
vision, weight gain, general numbness, broken bones in women; uncommon (may
affect up to 1 in 100 people): inflammation of the sinuses (sinusitis),
difficulty sleeping (insomnia) and bladder cancer; not known (frequency cannot
be estimated from the available data): increase in liver enzymes, allergic
reactions and eye diseases. It is not known whether these adverse effects were
the result of the metabolite MIN-102 or one of its metabolites.
Procedures: pain, minor bleeding, bruising, possible infection
Av. Ernest Lluch 32
Mataró (Barcelona) 08302
ES
Av. Ernest Lluch 32
Mataró (Barcelona) 08302
ES
Listed location countries
Age
Inclusion criteria
healthy male volunteers
18 - 55 yrs, inclusive
BMI: 18.0 - 28.0 kg/m2, inclusive
non-smoking
Exclusion criteria
Suffering from hepatitis B, hepatitis C, cancer or HIV/AIDS.
Participation in a drug study within 90 days prior to the first drug administration in the current study. Participation in more than 3 other drug studies (for male subjects) in the 10 months prior to (the first) drug administration in the current study.
Donation or loss of more than 100 mL of blood within 60 days prior to the first drug administration. Donation or loss of more than 1.5 liters of blood (for male subjects) in the 10 months prior to (the first) drug administration in the current study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-000607-82-NL |
| CCMO | NL57650.056.16 |