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Almorexant in Primary Insomnia

M

Midnight Pharma

Status and phase

Completed
Phase 1

Conditions

Insomnia
Primary Insomnia

Treatments

Drug: almorexant

Study type

Interventional

Funder types

Industry

Identifiers

NCT00640848
AC-057-103

Details and patient eligibility

About

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.

Enrollment

161 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Quadruple Blind

161 participants in 5 patient groups

1
Experimental group
Treatment:
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
2
Experimental group
Treatment:
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
3
Experimental group
Treatment:
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
4
Experimental group
Treatment:
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
5
Experimental group
Treatment:
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant
Drug: almorexant

Trial contacts and locations

27

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Data sourced from clinicaltrials.gov

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