First-in-human Study to Assess the Safety and Pharmacokin... | NCT02334449

NCT02334449

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2014-000937-22	EudraCT Number

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Single dose study part	Experimental	there will be 8 cohorts of healthy volunteers dosed with single doses of LML134 (8 planned dose levels) or with placebo and 2 potential additional cohorts (also dosed with single dose of LML134 or placebo)	Drug: LML134 Drug: Placebo
Multiple dose study part	Experimental	there will be 3 cohorts of healthy volunteers dosed with multiple doses of LML134 (3 planned dose levels) or placebo and one potential additional cohort (also dosed with multiple doses of LML134 or placebo)	Drug: LML134 Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
LML134	Drug	LML134 will be administered first as single doses and then as multiple doses	Multiple dose study part Single dose study part

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adverse events assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion	This safety outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatments.	Starting about 24 hours before dosing and continued until about 7-14 days after last dose
Cardiovascular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion	This safety outcome combines the measure of a set of cardiovascular safety parameters extracted from ECGs, 25 hours-Holter ECGs and from vital signs assessments	Starting about 24 hours before dosing and continued until about 7-14 days after last dose
Central nervous system safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion	This safety outcome combines the measure of a set of central nervous system safety parameters extracted from EEGs and neurological examinations	Starting about 24 hours before dosing and continued until about 7-14 days after last dose
Ocular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion	This safety outcome combined the measure of a set of ocular parameters including best corrected visual acuity and other parameters assessed by the mean of slit lamp biomicroscopy and dilated ophthalmoscopy examinations and by optical coherence tomography and electroretinography	Starting about 24 hours before dosing and continued until about 7-14 days after last dose
General safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK) of LML134: time to reach the maximum concentration after a single drug administration (Tmax) in Part 1 and in Part 3	Serum samples will be collected on Day 1: 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 2: 24h and 36h post dose, on Day 3: 48h and 60h post dose and on Day 4: 72h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above, in Parts 1 and 3. In Part 3, the outcome measure is done once without food intake and once after the intake of a high fat breakfast (in 2 different periods). Both outcomes (with and without breakfast intake) will be compared to assess the effect of a high fast breakfast on LML134 Tmax

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy male and female subjects age 18 to 55 years of age included, and in good health as determined by medical history, physical examination, vital signs, electrocardiogram, and laboratory tests.
Written informed consent must be obtained before any assessment is performed.
Able to communicate well with the Investigator, to understand and comply with the requirements of the study.

Exclusion Criteria:

History or presence of epilepsy or of seizures or convulsions of any kind.
Any clinically relevant abnormalities identified in the resting EEG during screening, or pre-ictal signs or other clinically relevant abnormalities in the hyperventilation or intermittent photic stimulation EEG during screening.
History of head trauma leading to clinically significant symptoms in the past two years.
Applies only to subjects enrolled in Part 2 MAD. Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
Significant illness including any clinically significant infectious disease which has not resolved within two (2) weeks prior to initial dosing.
History or presence of significant hematological abnormalities or immunodeficiency or any condition that might compromise the immune system (infection, vaccination), of any etiology as indicated by clinically significantly abnormal values of any of the following hematologic parameters: thrombocyte, RBC count, total WBC count and differentials presented as % of total white blood cell count and as absolute concentrations.
History or presence of any thyroid disease as indicated by any clinically relevant abnormality on thyroid stimulating hormone test (TSH).
History or presence of any chronic eye disease other than refractive error, strabismic amblyopia, or anisometropic amblyopia.
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.