Clinical trial NCT02334449: First-in-human Study to Assess the Safety and Pharmacokinetics of LML134 in Healthy Volunteers
Official title: A First-in-human, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Oral Dose Study, to Assess the Safety, Tolerability and Pharmacokinetics of LML134 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: healthy volunteers
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-01-08
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase I study to assess the safety, tolerability and pharmacokinetics of ascending single and multiple doses of the investigational medicinal product in healthy volunteers


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.

Primary outcomes:
measure: Adverse events assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
timeFrame: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
measure: Cardiovascular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
timeFrame: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
measure: Central nervous system safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
timeFrame: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
measure: Ocular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
timeFrame: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
measure: General safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
timeFrame: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
Secondary outcomes:
measure: Pharmacokinetics (PK) of LML134: time to reach the maximum concentration after a single drug administration (Tmax) in Part 1 and in Part 3
timeFrame: Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
measure: PK of LML134: Observed maximum serum concentration following single drug administration (Cmax) in Part 1 and Part 3
timeFrame: Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
measure: PK of LML134: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) in Part 1 and Part 3
timeFrame: Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
measure: PK of LML134: time to reach the maximum concentration after the first drug administration (Tmax) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
measure: PK of LML134: time to reach the maximum concentration after the last drug administration (Tmax) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
measure: PK of LML134: Observed maximum serum concentration following the first drug administration (Cmax) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
measure: PK of LML134: Observed maximum serum concentration following drug administration at steady state (Cmax,ss) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
measure: PK of LML134: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) after the first dose administration in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
measure: PK of LML134: The area under the serum concentration-time curve from time zero to the end of the dosing interval tau at steady state (AUCtau,ss) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
measure: PK of LML134: The average steady state serum concentration during multiple dosing (Cav,ss) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
measure: PK of LML134: The effective half-life based on drug accumulation at steady state (T1/2,acc) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
measure: PK of LML134: The accumulation ratio (Racc) in Part 2
timeFrame: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmceuticals
name: Study Director
role: STUDY_DIRECTOR
References: