Clinical trial NCT00640848: Almorexant in Primary Insomnia
Official title: Multi-center, Multiple-stage, Double-blind, Randomized, Placebo-controlled, Two-way Crossover, Single-dose Study to Investigate the Effects of ACT-078573 on Sleep Measured by Polysomnography in Patients With Primary Insomnia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insomnia
Primary Insomnia
Lead sponsor: Midnight Pharma, LLC
Sponsor class: INDUSTRY
First posted: 2008-03-21
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Sleep efficiency (%) assessed by PSG (polysomnography)
timeFrame: Between 10pm-12am (=lights out) until 480 minutes thereafter (=lights on)
Secondary outcomes:
measure: LPS (Latency to Persistent Sleep) [min] assessed by PSG (polysomnography)
timeFrame: Time from start of recording to the beginning of the first continuous 20 epochs of non-wake
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck, Dept. of Neurology Sleep Disorder Unit
city: Vienna
country: Austria
facility: Medical University of Vienna, Clinic of Neurology
city: Vienna
country: Austria
facility: Medical University of Vienna, University Clinic of Psychiatrie
city: Vienna
country: Austria
facility: The Siesta Group
city: Copenhagen
country: Denmark
facility: Scan Sleep
city: Glostrup
country: Denmark
facility: Glostrup University Hospital Department of Sleep Medicine
city: Espoo
country: Finland
facility: Skogby Sleep Clinic
city: Turku
country: Finland
facility: Sleep Research Unit, Dentalia, University of Turku
city: Berlin
country: Germany
facility: Charite Campus Benjamin Franklin, Klinik und Hochschulambulanz fur Psychiatrie and Psychotherapie
city: Berlin
country: Germany
facility: Department of Internal Medicine, Center for Sleep Medicine
city: Berlin
country: Germany
facility: St Hedwig-Krankenhaus, Akademisches Lehrkrankenhaus der Charite
city: Freiburg
country: Germany
facility: Department of Psychiatry and Psychotherapy of the University Hospital of Freiburg
city: Kiedrich
country: Germany
facility: St. Valentinushaus Klinik fur Psychiatrie und Psychotherapie
city: Marburg
country: Germany
facility: Universitatsklinikum Giessen und Marburg, Standort Marburg, Nervenklinik
city: Regensburg
country: Germany
facility: Klinik und Poliklinik fur Psychiatrie, Psychosomatik und Psychotherapie der Universitat am Bezirsklinikum
city: Schwerin
country: Germany
facility: SOMNIBENE Institut fur Medzinische Forschung und Schlafmedizin
city: Haifa
country: Israel
facility: Technion Sleep Medicine Center, Rambam Medical Center
city: Petah Tikva
country: Israel
facility: Assuta Medical Centers
city: Den Haag
country: Netherlands
facility: Medisch Centrum Haaglanden-Westeinde Ziekenhuis, Slaapcentrum (Holland Sleep Research)
city: Alzira
country: Spain
facility: Hospital de la Ribera
city: Barcelona
country: Spain
facility: Hospital de la Santa Crue/Sant Pau, Institut de Recerca
city: Skoevde
country: Sweden
facility: Skaraborg Hospital, Sleep Medicine Unit, Department of Neurorehabilitation
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Hospital, Sleep Disorder Unit
city: Basel
country: Switzerland
facility: Psychiatric University Clinics (UPK) Basel, Dept. for Depression Research, Sleep Medicine and Neurophysiology
city: Zurich
country: Switzerland
facility: University Hospital Zurich (USZ), Neurology Polyclinic, Center for Sleep Medicine
city: Edinburgh
country: United Kingdom
facility: The Edinburgh Sleep Centre
city: London
country: United Kingdom
facility: Medical Director, The London Sleep Centre
Study officials:
affiliation: Actelion
name: Jasper Dingemanse, PhD
role: STUDY_DIRECTOR
affiliation: Actelion
name: Eleornora Chiossi, MSc
role: STUDY_DIRECTOR
affiliation: Actelion
name: Petra Hoever, MSc
role: STUDY_DIRECTOR
affiliation: Actelion
name: Fabrice Kramer, MD
role: STUDY_DIRECTOR
affiliation: The Siesta Group
name: Georg Dorffner, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.