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

26. října 2016 aktualizováno: Novartis Pharmaceuticals

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

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

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

133

Fáze

  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Německo
      • Berlin, Německo, 14050
        • Novartis Investigative Site

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let až 55 let (Dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Intervenční model: Paralelní přiřazení
  • Maskování: Čtyřnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Single dose study part
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)
Lék: LML134
LML134 will be administered first as single doses and then as multiple doses
Lék: Placebo
All study cohorts (except food effect cohort) are placebo controlled
Experimentální: Multiple dose study part
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)
Lék: LML134
LML134 will be administered first as single doses and then as multiple doses
Lék: Placebo
All study cohorts (except food effect cohort) are placebo controlled

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Hodnocení nežádoucích účinků po podání jedné a více stoupajících dávek na začátku studie a opakovaně až do dokončení studie
Časové okno: Začněte přibližně 24 hodin před podáním dávky a pokračujte přibližně 7-14 dní po poslední dávce
Tento výsledek bezpečnosti kombinuje míru počtu subjektů, u kterých se vyskytly nežádoucí účinky (AE), povahu a závažnost těchto AE a jejich vztah ke studijní léčbě.
Začněte přibližně 24 hodin před podáním dávky a pokračujte přibližně 7-14 dní po poslední dávce
Cardiovascular safety assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion
Časové okno: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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
Časové okno: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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
Časové okno: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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
Časové okno: Starting about 24 hours before dosing and continued until about 7-14 days after last dose
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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Pharmacokinetics (PK) of LML134: time to reach the maximum concentration after a single drug administration (Tmax) in Part 1 and in Part 3
Časové okno: Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)

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

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 Cmax.
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
Časové okno: Starting 1hour prior to dosing on Day 1 and until 72 hours after dosing (Day 4)
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 AUClast.
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
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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 and on Day 2: 24h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
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
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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 post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
PK of LML134: Observed maximum serum concentration following the first drug administration (Cmax) in Part 2
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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 and on Day 2: 24h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
PK of LML134: Observed maximum serum concentration following drug administration at steady state (Cmax,ss) in Part 2
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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 post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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 and on Day 2: 24h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 24hr after the first dose administration on Day 2
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
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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 post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
PK of LML134: The average steady state serum concentration during multiple dosing (Cav,ss) in Part 2
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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 post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
PK of LML134: The effective half-life based on drug accumulation at steady state (T1/2,acc) in Part 2
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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 post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
PK of LML134: The accumulation ratio (Racc) in Part 2
Časové okno: Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)
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 post dose, on Day 3: 1hr prior the second dose administration, on Days 4, 5, 6, 8, 10, 12, 13, 14: 1hr prior dosing, on Day 15 (last time the drug is administered): 1hr predose; 0,25h; 0,5h; 1h; 1,5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h post dose, on Day 16: 24h post dose and Day 17: 48h post dose. This outcome measure shows the mean of all subject values resulting from each time point specified above.
Starting 1hour prior the first dose administration (Day 1) until 48hour after the last dose administration (Day 17)

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Novartis Pharmaceuticals

Vyšetřovatelé

  • Ředitel studie: Study Director, Novartis Pharmceuticals

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. února 2015

Primární dokončení (Aktuální)

1. února 2016

Dokončení studie (Aktuální)

1. února 2016

Termíny zápisu do studia

První předloženo

14. listopadu 2014

První předloženo, které splnilo kritéria kontroly kvality

6. ledna 2015

První zveřejněno (Odhad)

8. ledna 2015

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

27. října 2016

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

26. října 2016

Naposledy ověřeno

1. října 2016

Více informací

Termíny související s touto studií

Klíčová slova

Další identifikační čísla studie

  • CLML134X2101
  • 2014-000937-22 (Číslo EudraCT)

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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