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Completed

NCT Number: NCT02571855

A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of ACT-541468 in Healthy Young Adults and Elderly Subjects

The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics (PK, or amount of drug over time in the body) and pharmacodynamics (PD, or effects on the body) of ACT-541468 following multiple ascending doses in healthy adults and following single ascending doses in healthy elderly subjects when administered in the morning. The safety, PK and PD of ACT-541468 will also be assessed after repeated evening administration of a selected dose in both healthy adults and elderly.

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Key information

Conditions

Healthy Subjects Dyssomnias Mental Disorders Nervous System Diseases Sleep Disorders, Intrinsic Sleep Initiation and Maintenance Disorders Sleep Wake Disorders

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Investigator Site

Leiden, Netherlands

About this study

In the first-in-man study, single doses of ACT-541468 administered in healthy young adults were well tolerated up to the dose level of 200 mg (inclusive) and yielded results compatible with possible sleep facilitating effects of ACT-541468. So the present study aimed to further investigate the effects of ACT-541468 after multiple ascending doses in healthy young subjects as well as after single ascending doses in elderly subjects (morning administrations). The effects of repeated administrations of a selected dose administered in the evening in both healthy adults and elderly, will also be investigated.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed informed consent.
  • Adults aged from 18 to 45 years (inclusive) for Part A; elderly aged from 65 to 80 years (inclusive) for Part B; both adults from 18 to 45 years and elderly from 65 to 80 years (inclusive) for Part C.
  • Regular sleep pattern of at least 6 hours nocturnal sleep.
  • Young females must have negative pregnancy tests at screening and at pre-dose on Day 1 and use a reliable method of contraception
  • Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
  • Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) between 100-145 mmHg, 50-90 mmHg and 45-90 bpm (all inclusive) for young adults, respectively; SBP, DBP and PR between 100-160 mmHg, 50-95 mmHg and 45-100 bpm (all inclusive) for elderly, respectively.
  • Healthy on the basis of physical examination,electrocardiogram and laboratory tests.

Exclusion criteria

Principal exclusion criteria common to young adults and elderly:

  • Pregnant or lactating women.
  • Any contraindication to the study drugs.
  • History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs.
  • History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0 at screening.
  • Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.

Exclusion criteria

for young adults only:

  • Treatment with any prescribed medications or over-the-counter medications within 2 weeks prior to study drug administration.

Exclusion criteria

for elderly only:

  • Previous chronic treatment with any medication that is not given in stable doses and/or stable regimen within 2 months prior to screening.
  • Previous treatment with CNS-active drugs or within 2 months prior to screening.
  • Treatment with inhibitors of CYP3A4 (e.g., azole derivatives, ritonavir, clarithromycin) from 2 weeks prior to screening visit and up to EOS.

Treatment and study plan

ACT-541468 (hydrochloride salt)

Drug

Hard-gelatin capsules (strength: 5 mg and 25 mg)

ACT-541468 (free base)

Drug

Soft capsules (strength: 25 mg)

Placebo

Drug

Placebo capsules matching the ACT-541468 formulations

Primary outcomes

  1. Number of participants with Adverse Events (AEs)

    Time frame: up to 72 hours post dosing

    Treatment emergent adverse events and treatment emergent serious adverse events will be evaluated throughout the study

  2. Changes from baseline in ECG variables and vital signs (heart rate and blood pressure)

    Time frame: up to 72 hours post dosing

    12-lead electrocardiogram variables including RR, PR, QRS, QT and QTc intervals at scheduled time points during Parts A, B and C

  3. Changes from baseline in clinical laboratory parameters

    Time frame: up to 72 hours post dosing

    Laboratory tests including hematology, blood chemistry and urinalysis at scheduled time points during PArts A, B and C

Secondary outcomes

  1. Maximum plasma concentration (Cmax) of ACT-541468 after daytime and bedtime intake

    Time frame: Part A: Day 1 and Day 5; Part B: Day 1; Part C: evening of Day 8 (pre-dose) and Day 9 (nighttime samples)

    Cmax will be determined after single (Parts A and B) and multiple morning doses (Part A) as well as after repeated evening doses to identify the nighttime PK profile (Part C)

  2. Time to reach Cmax (tmax) of ACT-541468 after daytime and bedtime intake

    Time frame: Part A: Day 1 and Day 5; Part B: Day 1; Part C: evening of Day 8 (pre-dose) and Day 9 (nighttime samples)

    tmax will be determined after single (Parts A and B) and multiple morning doses (Part A) as well as after repeated evening doses to identify the nighttime PK profile (Part C)

  3. Terminal half-life [t(1/2)] after daytime and bedtime intake

    Time frame: Part A: Days 1 and 5, from pre-dose up to 72 h post-dose; Part B: Day 1, at pre-dose up to 72 h post-dose; Part C: from the morning of Day 8 up to 60 h post-dose and from the evening of Day 8 (pre-dose) until 36 h post-dose (with nighttime samples)

    t(1/2) will be determined after single (Parts A and B) and multiple morning doses (Part A) as well as after repeated evening doses (Part C)

  4. Areas under the plasma concentration-time curves [AUC(0-8), AUC(0-24)] of ACT-541468 after daytime and bedtime intake

    Time frame: Part A: Days 1 and 5, from pre-dose up to 72 h post-dose; Part B: Day 1, at pre-dose up to 72 h post-dose; Part C: from the morning of Day 8 up to 60 h post-dose and from the evening of Day 8 (pre-dose) until 36 h post-dose (with nighttime samples)

    AUC from time 0 to 8 hours after study drug administration [AUC(0--8)] and from time 0 to 24 hours after study drug administration [AUC(0--24)] will be determined after single (parts A and B) and multiple morning doses (Part A) as well as after multiple evening doses (Part C)

  5. Areas under the plasma concentration-time curves [AUC(0-t), AUC(0-inf)] of ACT-541468 after daytime and bedtime intake

    Time frame: Part A: Day 5, from pre-dose up to 72 h post-dose; Part B: Day 1, at pre-dose up to 72 h post-dose; Part C: from the morning of Day 8 up to 60 h post-dose and from the evening of Day 8 (pre-dose) until 36 h post-dose (with nighttime samples)

    AUC from time 0 to infinity [AUC(0--inf], AUC from time 0 to time of the last measured concentration above the limit of quantification [AUC(0--t)] will be determined after single (Part B) and multiple morning doses (Part A) as well as after multiple evening doses (Part C)

  6. Sedation as measured by saccadic peak velocity

    Time frame: Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14

    saccadic eye movements (SEM) will be recorded by electrooculography and the average values of saccadic peak velocity of the SEM will be used as parameter of sedation

  7. Visual motor coordination

    Time frame: Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14

    Visual motor coordination will be assessed with the adaptive tracking test and the average tracking performance will be used as parameter of coordination

  8. Change from baseline in body sway

    Time frame: Part A: Day 1 and Day 5; Part B: Day 1; Part C: Day 2 and Day 14

    Body sway will be assessed using a body sway meter

  9. Change from baseline in subjective cognitive effects

    Time frame: Part A: every day from Day 1 to Day 6; Part B: Day 1; Part C: Day 1 to Day 8

    Subjects will rate sleepiness, alertness and mood using questionnaires

Sponsors and collaborators

Lead sponsor

Idorsia Pharmaceuticals Ltd.

Industry

Registry information

Official study title

Double-blind, Placebo-controlled, Randomized Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-541468: Part A: Multiple-ascending Doses in Healthy Young Adults After Morning Administration Part B: Single-ascending Doses in Healthy Elderly Subjects After Morning Administration Part C: Repeated Doses in Both Healthy Young Adults and Elderly Subjects After Evening Administration

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Oct 8, 2015
Registry last updated
Jul 10, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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