First-in-human Study to Assess the Safety and Pharmacokinetics of LML134 in Healthy Volunteers

NCT02334449 | Completed Phase 1

• 2 other identifiers: CLML134X21012014-000937-22
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Volunteers

Keywords

healthy volunteers

Outcome Measures

Primary Outcomes (5)

• 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

  This general safety outcome combines the measure of blood laboratory parameters and the outcome of physical examinations

  Starting about 24 hours before dosing and continued until about 7-14 days after last dose

Secondary Outcomes (12)

• Pharmacokinetics (PK) of LML134: time to reach the maximum concentration after a single drug administration (Tmax) in Part 1 and in Part 3

  Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)

• PK of LML134: Observed maximum serum concentration following single drug administration (Cmax) in Part 1 and Part 3

  Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)

• 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

  Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)

• PK of LML134: time to reach the maximum concentration after the first drug administration (Tmax) in Part 2

  Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2

• PK of LML134: time to reach the maximum concentration after the last drug administration (Tmax) in Part 2

  Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)

Study Arms (2)

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

Interventions

LML134 DRUG

LML134 will be administered first as single doses and then as multiple doses

Multiple dose study part; Single dose study part

Placebo DRUG

All study cohorts (except food effect cohort) are placebo controlled

Multiple dose study part; Single dose study part

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Berlin, 14050, Germany

Location

Study Officials

• Study Director

  Novartis Pharmceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2014
• First Posted: January 8, 2015
• Study Start: February 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: October 27, 2016

Record last verified: 2016-10

Locations

DE (1)