Sodium Oxybate in Idiopathic Hypersomnia (SODHI)

A Randomized, Double-blind, Placebo-controlled Trial Comparing the Efficacy and Tolerance of Sodium Oxybate in Patients Affected With Idiopathic Hypersomnia

this study evaluates of the efficacy of sodium oxybate on excessive daytime sleepiness using Epworth sleepiness scale over 8 weeks compared to placebo

Study Overview

• Status: Completed
• Conditions: Idiopathic Hypersomnia
• Intervention / Treatment: Drug: Sodium Oxybate Oral Solution 500 MG/ML; Drug: Placebos

Detailed Description

Bicentric, randomized, double-blind controlled study Outpatients aged from 18 to 60 years, suffering from current idiopathic hypersomnia (ICSD-3), recruited via medical consultations in the investigation centers Randomization in Xyrem or placebo arms after the inclusion visit,

1.Screening Period (up to 15 days), 2.Titration Period (up to 45 days), 3.Maintenance Period (minimum 15 days), 4.Safety Follow-Up Period (14 days)

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yves DAUVILLIERS, Pr; Phone Number: 33 4 67 33 63 61; Email: y-dauvilliers@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France
    • University Hospital of Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnostic of idiopathic hypersomnia (ICSD-3 criteria)
• Age between 18 and 60 years-old
• BMI between 18 and 35 kg/m2
• MSLT: mean sleep latency (MSL) ≤8 minutes and < 2 SOREMPs, AND/OR total sleep time > 11h/24h on 24-hours long-term polysomnography
• Polysomnography recording: sleep efficiency > 85%, total sleep time ≥6 hours, AHI <10/hour, micro-arousals index <15/hour, PLM index associated with micro-arousals <10/hour.
• Absence of sleep deprivation, assessed by actigraphy or sleep logs
• ESS score ≥14 points
• Written informed consent
• National health insurance cover

Exclusion Criteria:

• Current alcohol intake or treatment with modafinil, amphetamine, methylphenidate, mazindol, pitolisant, neuroleptics, sedative hypnotics, barbiturates, general anesthetics, myorelaxants, other CNS depressants, antidepressants*, anxiolytic drugs, anticonvulsive therapy, topiramate, inhibitors of GHB dehydrogenase (i.e. valproate, ethosuximide, phenytoin), budipine, dopamine antagonist antiemetics (except domperidone), opioids, benzodiazepines, Z-drugs, MAO inhibitors, COMT inhibitors, or sedative antihistamines. If patient has received such therapy, a washout-period of at least 15 days, or equivalent to 5 half-lives of the drug, prior to the inclusion in the study is required before starting treatment in this study.

  *30 days for antidepressants

• Previous intake of sodium oxybate
• Succinic semialdehyde dehydrogenase deficiency, porphyria
• Other central nervous system diseases: neurodegenerative diseases, seizure disorders or history of head trauma associated with loss of consciousness
• Lifetime history of suicide attempt or suicidal ideation in the past 6 months, prior history of psychotic episodes, current or recent history of a major depressive disorder (DSM-V), Beck depression inventory (BDI) > 16 and/or item G> 0
• History of chronic alcohol or drug abuse within the prior 12 months
• Malignant neoplastic disease requiring therapy within 12 months prior to Visit 1 or clinically relevant
• Heart failure, severe hypertension or other cardiovascular disease compromising the patient's wellbeing or ability to participate in this study
• Renal or hepatic impairment Compromised respiratory function
• Sleep-related breathing disorders (AHI ≥ 10/h)
• No regular sleep at night: shift work or other continuous non-disease-related life conditions
• Participation in another study of an investigational drug within the 28 days prior to Visit 1 or currently
• Hypersensitivity to any of the components of the study medication
• Pregnancy (βHCG positive) and breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xyrem; Xyrem (Sodium Oxybate), oral solution 500mg/mL First night after V1: Dose prescribed at 4.5 g per night (2.25 g x 2) for 2 weeks First night after V2: Dose increased to 6 g per night (3 g x 2) for 2 weeks, according to investigator's opinion, tolerance of drug and CGI-S First night after V3: Dose either maintained stable at 6 g or increased to 9 g per night (4.5 g x 2) with dose increments of 1.5 g per night (0.75 g x 2) every week, based on benefit-risk ratio, for 2 weeks. First night after V4: Dose maintained at 9 g or reduced at 6 g per night according to benefit-risk ratio for 2 weeks. No dose adjustment during the Maintenance period. First night after V5: Taper period. Dose decrease by 2.25 g x 2 every two days until complete withdrawal	Drug: Sodium Oxybate Oral Solution 500 MG/ML; First night after V1: Dose prescribed at 4.5 g per night (2.25 g x 2) for 2 weeks First night after V2: Dose increased to 6 g per night (3 g x 2) for 2 weeks, according to investigator's opinion, tolerance of drug and CGI-S First night after V3: Dose either maintained stable at 6 g or increased to 9 g per night (4.5 g x 2) with dose increments of 1.5 g per night (0.75 g x 2) every week, based on benefit-risk ratio, for 2 weeks. First night after V4: Dose maintained at 9 g or reduced at 6 g per night according to benefit-risk ratio for 2 weeks. No dose adjustment during the Maintenance period. First night after V5: Taper period. Dose decrease by 2.25 g x 2 every two days until complete withdrawal
Placebo Comparator: Placebos; Xyrem Placebo: sodium citrate solution in equimolar concentration of sodium in the 500 mg/mL Xyrem oral solution, PH adjusted with malic acid	Drug: Placebos; Xyrem Placebo: sodium citrate solution in equimolar concentration of sodium in the 500 mg/mL Xyrem oral solution, PH adjusted with malic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epworth Sleepiness Scale (ESS) score at the end-point visit	Evaluation of difference in sleepiness with ESS between the 2 groups. ESS scores range from 0 to 24; there is a risk of pathological daytime sleepiness if score is > 10.	over 8 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Yves DAUVILLIERS, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2018
• Primary Completion (Actual): April 12, 2023
• Study Completion (Actual): April 12, 2023

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Idiopathic Hypersomnia
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Idiopathic Hypersomnia; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Adjuvants, Anesthesia; Sodium Oxybate
• Other Study ID Numbers: RECHMPL17_0375

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No