Almorexant in Primary Insomnia

NCT ID: NCT00640848

Last Updated: 2016-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2007-09-30

Brief Summary

The aim of the study is to determine the minimum effective dose of ACT-078573 on sleep efficiency and to assess the effects of different doses of ACT-078573 on other PSG parameters.

Conditions

Insomnia; Primary Insomnia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: EXPERIMENTAL

almorexant

Intervention Type: DRUG

1 dose of 400 mg in two treatment sequences

2

Group Type: EXPERIMENTAL

almorexant

Intervention Type: DRUG

1 dose of 200 mg in two treatment sequences

3

Group Type: EXPERIMENTAL

almorexant

Intervention Type: DRUG

1 dose of 100 mg in two treatment sequences

4

Group Type: EXPERIMENTAL

almorexant

Intervention Type: DRUG

1 dose of 50 mg mg in two treatment sequences

5

Group Type: EXPERIMENTAL

almorexant

Intervention Type: DRUG

1 dose of 1000 mg in two treatment sequences

Interventions

almorexant

1 dose of 400 mg in two treatment sequences

Intervention Type: DRUG

almorexant

1 dose of 200 mg in two treatment sequences

Intervention Type: DRUG

almorexant

1 dose of 100 mg in two treatment sequences

Intervention Type: DRUG

almorexant

1 dose of 50 mg mg in two treatment sequences

Intervention Type: DRUG

almorexant

1 dose of 1000 mg in two treatment sequences

Intervention Type: DRUG

Other Intervention Names

ACT-078573; ACT-078573; ACT-078573; ACT-078573; ACT-078573

Eligibility Criteria

Inclusion Criteria

• Men or women 18 - 65 years of age (inclusive).
• Women of childbearing potential must have a negative urine pregnancy test at the screening visit, the screening adaptation night, and pre-treatment and use a reliable method of contraception during the entire study duration and for at least 3 months after study drug intake.

Reliable methods of contraception are:

• Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.
• Intra-uterine devices.
• Oral, injectable, implantable or transdermal contraceptives only in combination with a barrier method.

• Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.

Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.

• Body mass index (BMI) between 18 and 30 kg/m2 (limits included) at screening visit.
• 12-lead ECG without clinically relevant abnormalities at screening visit.
• Hematology and biochemistry test results not deviating from the normal range to a clinically relevant extent at screening visit and following the screening/adaptation night.
• Primary insomnia by DSM-IV-TR criteria based on medical history and the assessments performed at screening visit.
• History of the following for at least 3 months prior to the screening visit:

• Usual reported subjective total sleep time (TST) 3 - 6 hours.
• Usual sleep disturbance with a subjective sleep onset latency of > 30 min.
• Daytime complaints associated with poor sleep (e.g., fatigue, irritability, difficulty concentrating).
• Polysomnography (PSG) at screening/adaptation night confirming TST < 6 h and LPS ≥ 20 min.
• Willingness to refrain from CNS-active drugs for 5 half-lives of the respective drug (but at least 1 week) prior to the screening/adaptation night and up to the end of treatment period 2. The usage of short-acting hypnotics (defined as hypnotics with a half-life of up to and including 10 hours) is allowed up to 48 hours prior to each PSG night, i.e., prior to the screening/adaptation night and prior to the treatment PSG nights.
• Urine drug test negative for barbiturates, cannabinoids, amphetamines, and cocaine at screening visit 1, screening/adaptation PSG night and pre-treatment. Urine drug test negative for benzodiazepines and opiates at screening/adaptation PSG night and pre-treatment.
• Signed informed consent prior to any study-mandated procedure.

Exclusion Criteria

• Symptom assessment questionnaire (SBB) for diagnosis of apnea resulting in a score > 2 at screening visit.
• Zung self-rating depression scale (SDS) and/or Zung self-rating anxiety scale (SAS) resulting in a raw score ≥ 50 at screening visit.
• Restless legs syndrome and/or meeting all four essential diagnostic criteria for RLS (see Appendix 10).
• Insomnia due to sleep apnea or periodic limb movement disorder as assessed by PSG at screening/adaptation night:

• apnea/hypopnea index (AHI) > 10/h
• periodic limb movement arousal index > 10/h
• Major depressive disorder, severe psychosis, or significant anxiety disorder.
• Pregnancy or breast-feeding.
• Systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg at screening visit.
• Within the 2-month period prior to the screening visit, clinical evidence of alcoholism or drug abuse.
• Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as psychiatric disease or a disease which may affect the pharmacokinetics of the study drug.
• Treatment with strong inhibitors of CYP3A4 (e.g., azole derivatives, ritonavir, clarithromycin) within 1 week prior to the screening/adaptation PSG night and up to the end of treatment period 2.
• Excessive caffeine consumption (regular caffeine consumption of > 7 units per day).
• Night shift workers.
• Known hypersensitivity to any excipients of the drug formulation.
• Planned treatment or treatment with another investigational drug within 1 month prior to randomization and up to the end of treatment period 2.
• Known concomitant life-threatening disease with a life expectancy < 24 months.
• Unstable medical abnormality, significant medical disorder or acute illness.
• Recruitment of the same patient twice to the same dose level. Patients may be recruited to a lower dose level, provided that there are at least 28 days between last study drug administration and screening/adaptation PSG night.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Midnight Pharma, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Actelion

Principal Investigators

Jasper Dingemanse, PhD

Role: STUDY_DIRECTOR

Actelion

Eleornora Chiossi, MSc

Role: STUDY_DIRECTOR

Actelion

Petra Hoever, MSc

Role: STUDY_DIRECTOR

Actelion

Fabrice Kramer, MD

Role: STUDY_DIRECTOR

Actelion

Georg Dorffner, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

The Siesta Group

Locations

Medical University of Innsbruck, Dept. of Neurology Sleep Disorder Unit

Innsbruck, , Austria

Medical University of Vienna, Clinic of Neurology

Vienna, , Austria

Medical University of Vienna, University Clinic of Psychiatrie

Vienna, , Austria

The Siesta Group

Vienna, , Austria

Scan Sleep

Copenhagen, , Denmark

Glostrup University Hospital Department of Sleep Medicine

Glostrup Municipality, , Denmark

Skogby Sleep Clinic

Espoo, , Finland

Sleep Research Unit, Dentalia, University of Turku

Turku, , Finland

Charite Campus Benjamin Franklin, Klinik und Hochschulambulanz fur Psychiatrie and Psychotherapie

Berlin, , Germany

Department of Internal Medicine, Center for Sleep Medicine

Berlin, , Germany

St Hedwig-Krankenhaus, Akademisches Lehrkrankenhaus der Charite

Berlin, , Germany

Department of Psychiatry and Psychotherapy of the University Hospital of Freiburg

Freiburg im Breisgau, , Germany

St. Valentinushaus Klinik fur Psychiatrie und Psychotherapie

Kiedrich, , Germany

Universitatsklinikum Giessen und Marburg, Standort Marburg, Nervenklinik

Marburg, , Germany

Klinik und Poliklinik fur Psychiatrie, Psychosomatik und Psychotherapie der Universitat am Bezirsklinikum

Regensburg, , Germany

SOMNIBENE Institut fur Medzinische Forschung und Schlafmedizin

Schwerin, , Germany

Technion Sleep Medicine Center, Rambam Medical Center

Haifa, , Israel

Assuta Medical Centers

Petah Tikva, , Israel

Medisch Centrum Haaglanden-Westeinde Ziekenhuis, Slaapcentrum (Holland Sleep Research)

The Hague, , Netherlands

Hospital de la Ribera

Alzira, , Spain

Hospital de la Santa Crue/Sant Pau, Institut de Recerca

Barcelona, , Spain

Skaraborg Hospital, Sleep Medicine Unit, Department of Neurorehabilitation

Skövde, , Sweden

Uppsala Akademiska Hospital, Sleep Disorder Unit

Uppsala, , Sweden

Psychiatric University Clinics (UPK) Basel, Dept. for Depression Research, Sleep Medicine and Neurophysiology

Basel, , Switzerland

University Hospital Zurich (USZ), Neurology Polyclinic, Center for Sleep Medicine

Zurich, , Switzerland

The Edinburgh Sleep Centre

Edinburgh, , United Kingdom

Medical Director, The London Sleep Centre

London, , United Kingdom

Countries

Austria; Denmark; Finland; Germany; Israel; Netherlands; Spain; Sweden; Switzerland; United Kingdom

References

Hoever P, Dorffner G, Benes H, Penzel T, Danker-Hopfe H, Barbanoj MJ, Pillar G, Saletu B, Polo O, Kunz D, Zeitlhofer J, Berg S, Partinen M, Bassetti CL, Hogl B, Ebrahim IO, Holsboer-Trachsler E, Bengtsson H, Peker Y, Hemmeter UM, Chiossi E, Hajak G, Dingemanse J. Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial. Clin Pharmacol Ther. 2012 Jun;91(6):975-85. doi: 10.1038/clpt.2011.370.

Reference Type: DERIVED

PMID: 22549286 (View on PubMed)

Other Identifiers

AC-057-103

Identifier Type: -

Identifier Source: org_study_id