Trial of Effects of Oral Xyrem and Zolpidem on Sleep-Diso... | NCT00086281

NCT00086281

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Experimental	Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later	Drug: Xyrem (X)
2	Active Comparator	Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.	Drug: Zolpidem (Z) Drug: Placebo (P)
3	Experimental	Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment).	Drug: Xyrem (X) Drug: Modafinil (M)
4	Placebo Comparator	Placebo was given at bedtime and again 2.5 to 4 hours later.	Drug: Placebo (P)

Name	Type	Description	Arm Group Labels	Other Names
Xyrem (X)	Drug	Xyrem (Sodium Oxybate) Oral Solution	1 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Primary Efficacy Variable Was the Mean Apnea-Hypopnea Index (AHI).	The AHI was defined as the incidence(events per hour) of apnea and hypopnea events associated with sleep, determined from the overnight polysomnogram (PSG). An apnea event is characterized by a cessation in airflow lasting >= 10 seconds, accompanied by oxygen desaturation of >3% or arousal. An Hyponea event is characterized by a transient reduction in breathing lasting >= 10 seconds, with clear decrease (>50%) from baseline in the amplitude of breathing or a decrease <50% in the amplitude of breathing accompanied by oxygen desaturation of >3% or arousal.	One night of PSG during one night of treatment each per arm.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed and dated an informed consent prior to beginning protocol required procedures.
Willing and able to complete the entire trial as per the protocol including 6 nights in the sleep lab.
18 years of age or older.
Have a history of obstructive sleep apnea syndrome (as per American Academy of Sleep Medicine [AASM] Task Force 1999).
Apnea-Hypopnea Index(AHI): 10 to 40 inclusive, lowest O2 saturation ≥75% (see AASM Task Force 1999 criteria)
Females may be included who are surgically sterile, two years post-menopausal, or if of child-bearing potential, using a medically accepted method of birth control (e.g., barrier method with spermicide, oral contraceptive, or abstinence) and agree to continue use of this method for the duration of the trial.
In the opinion of the investigator have adequate support for the duration of the trial to include transportation to and from the trial site. In addition, if in the investigator's assessment it is clinically indicated, the patient is willing to not operate a car or heavy machinery for the duration of the trial or for as long as the investigator deems clinically indicated.

Exclusion Criteria:

Have taken sodium oxybate (GHB) in the last 30 days.
Have taken any investigational therapy within the 30-day period prior to the initial screening visit for this trial.
Are routinely taking any stimulant medications, sedative hypnotics, tranquilizers, antihistamines (except for non-sedating antihistamines), benzodiazepines or clonidine at the start of the study. Patients taking anticonvulsants are not eligible to participate even if they are willing to washout anticonvulsants for the trial.
Regularly consume alcohol and are unwilling or unable to totally abstain from alcohol use for the trial duration.
Are experiencing any major illness, including unstable cardiovascular, endocrine, neoplastic, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurological, pulmonary, and/or renal disease which would place the patient at risk during the trial or compromise the objectives outlined in the protocol.
Have psychiatric disorders, major affective or psychotic disorders, or other problems that, in the investigator's opinion, would preclude the patient's participation and completion of this trial or compromise reliable representation of subjective symptoms.
Have a current or recent (within one year) history of a substance use disorder including alcohol abuse as defined by the DSM-IV.
Have a serum creatinine greater than 2.0 mg/dL, abnormal liver function tests (SGOT [AST] or SGPT [ALT] more than twice the upper limit of normal), or elevated serum bilirubin (more than 1.5 times the upper limit of normal), or pre-trial ECG results demonstrating clinically significant arrhythmias, greater than a first degree AV block or a history of myocardial infarction within the last six months.
Have an occupation that requires variable shift work or routine night shift.
Have a clinically significant history of seizure disorder either past or present, a history of clinically significant head trauma (i.e., concussion resulting in clinically significant loss of consciousness) or past invasive intracranial surgery, and are taking anticonvulsant medications.

Name	Affiliation	Role
Yanping Zheng, MD	Jazz Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Research Group of St. Petersburg		St. Petersburg	Florida	33707	United States
London Health Sciences Centre, Victoria Campus

PubMed Identifier	Type	Citation	Retractions
11833860	Background	A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep. 2002 Feb 1;25(1):42-9.
12627729	Background	A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. Sleep. 2003 Feb 1;26(1):31-5.

Arm/Group Information

ID	Title	Description
FG000	P Then X Then Z With P Then X With M	Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment).
FG001	X Then X With M Then P Then Z With P	Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment); then Placebo was given at bedtime and again 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.
FG002	X With M Then Z With P Then X Then P	Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment); then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later; then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Placebo was given at bedtime and again 2.5 to 4 hours later.
FG003	Z With P Then P Then X With M Then X	Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later; then Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment); then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later.
FG004	P Then X Then P Then X With M Then Z With P	Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment); then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.
FG005	X Then Z With P Then X With M Then P	Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment); then Placebo was given at bedtime and again 2.5 to 4 hours later.
FG006	X Then Z With P Then P Then X With M	Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later; then Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment).
FG007	X Then X Then P Then Z With P	Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Placebo was given at bedtime and again 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.
FG008	X With M Then X Then P Then Z With P	Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment); then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Placebo was given at bedtime and again 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.
FG009	P Then X Then Z With P	Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.
FG010	Z With P Then P Then X With M	Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later; then Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment).
FG011	P Then X	Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later.
FG012	Placebo	Placebo was given at bedtime and again 2.5 to 4 hours later
FG013	Xyrem	Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later.
FG014	X With M	Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment).

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	P Then X Then Z With P Then X With M	Placebo was given at bedtime and again 2.5 to 4 hours later; then Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; then Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later; then Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment).

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Primary Efficacy Variable Was the Mean Apnea-Hypopnea Index (AHI).

The AHI was defined as the incidence(events per hour) of apnea and hypopnea events associated with sleep, determined from the overnight polysomnogram (PSG). An apnea event is characterized by a cessation in airflow lasting >= 10 seconds, accompanied by oxygen desaturation of >3% or arousal. An Hyponea event is characterized by a transient reduction in breathing lasting >= 10 seconds, with clear decrease (>50%) from baseline in the amplitude of breathing or a decrease <50% in the amplitude of breathing accompanied by oxygen desaturation of >3% or arousal.

Posted

Mean

Standard Deviation

Apnea + Hypopnea episodes per hour

One night of PSG during one night of treatment each per arm.

ID	Title	Description
OG000	Placebo	Placebo
OG001

Adverse Events Module

ID	Term
D020181	Sleep Apnea, Obstructive
D012891	Sleep Apnea Syndromes

ID	Term
D001049	Apnea
D012120	Respiration Disorders
D012140	Respiratory Tract Diseases
D020919	Sleep Disorders, Intrinsic

ID	Term
D006885	Hydroxybutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids

ID	Term
D012978	Sodium Oxybate
D000077334	Zolpidem
D000077408	Modafinil