Single- and Multiple-Dose Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Sodium Oxybate (Xyrem®) in Subjects with Moderate to Severe Essential Tremor

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-002222-30-FR
• Date of registration: 24/07/2007
• Prospective Registration: Yes
• Primary sponsor: Jazz Pharmaceuticals Inc.
• Public title: Single- and Multiple-Dose Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Sodium Oxybate (Xyrem®) in Subjects with Moderate to Severe Essential Tremor
• Scientific title: Single- and Multiple-Dose Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Sodium Oxybate (Xyrem®) in Subjects with Moderate to Severe Essential Tremor
• Date of first enrolment: 28/08/2007
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002222-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: open in the first part, then double-blind in the second part; Cross-over in the second part only If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

France

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of moderate or severe classic essential tremor (bilateral, largely symmetric postural or kinetic tremor involving hands and forearms that is visible and persistent). with a score of 2 to 4 on the Fahn-Tolosa-Marin Essential Tremor Rating Scale
2. Male and female subjects age 50 to 75 years, inclusive.
3. Inability to reproduce a nearly perfect spiral drawing using the hand that experiences the more severe tremor (tremor is not necessarily better or worse in the dominant hand).
4. Willingness and ability to safely stop and remain off any medications used to treat ET for at least five half-lives prior to Day 1 and for the duration of the study.
5. Willingness to abstain from ethanol and caffeine intake for at least 48 hours prior to Days 1 and 4 and on inpatient days.
6. Good general health as determined by physical examination, medical history, clinical laboratory findings, and ECG at screening, as determined by the investigator.
7. Consent to use a medically acceptable method of contraception throughout the entire study period and for 1 week after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or the partner include abstinence, birth control pills or patches or vaginal ring, diaphragm and spermicide, intrauterine device (IUD), condom and vaginal spermicide, surgical sterilization, post-menopausal partner, vasectomy (>6 months prior to baseline), and progestin implant or injection.
8. Negative screens for HIV Ab, HbsAg, and HCV-Ab and no history of a positive result.
9. Negative urine drug and alcohol screens at screening and baseline (Day -1).
10. Hemoglobin of 12.0 g/dL or greater.
11. Ability to read, understand, and provide written informed consent before enrolling in the study, and willingness to comply with all study procedures.
12. Agreement to remain in the study facility for approximately 6 study days.
13. Negative pregnancy test for all females at screening and baseline (Day -1).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects with a clinically significant unstable medical abnormality, chronic disease, or history or presence of significant hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, psychiatric, or metabolic disease or any other abnormality (other than essential tremor) that could interfere with the pharmacokinetic evaluation of the study drug.
2. Subjects with succinic semialdehyde dehydrogenase deficiency (SSDD).
3. Subjects currently taking primidone (Mysoline®).
4. Subjects with any severe drug allergy or a history of allergic or severe adverse reactions or intolerance to sodium oxybate.
5. Subjects who are on sodium-restricted diets.
6. Subjects who are color blind.
7. Subjects with deep brain stimulators (DBSs).
8. Subjects with a known history of sleep apnea.
9. Subjects who have previously used Xyrem® or GHB (gamma hydroxybutyrate).
10. Subjects with clinically significant illness within 30 days of screening, as determined by the investigator.
11. Subjects with a clinically significant abnormal finding (other than essential tremor) on physical examination, ECG, or clinical laboratory tests, as determined by the investigator.
12. Females who are pregnant, breastfeeding, or lactating.
13. Subjects who self-report ingestion of alcohol ingestion within 48 hours prior to dosing through completion of the study.
14. Subjects who self-report significant abuse of tobacco (>10 cigarettes or equivalent per day), analgesics, tranquilizers, opioids, mood-altering drugs, or known drug dependence prior to Day -1, or have used tobacco products or products, including nicotine-containing products, for smoking cessation within 90 days before screening.
15. Subjects who used any prescription medication within 14 days or over-the-counter (OTC) medication within 7 days of randomization or intends to use any prescription or OTC medication during the study that may interfere with the evaluation of the study drug. Exceptions, to be discussed with the medical monitor prior to admission to the study, can include stable doses of: cholesterol-reducing medications and hormonal replacement therapy.
16. Subjects who used any other investigational drug within 30 days or five half-lives (whichever is longer) before dosing, or plans to use an investigational drug (other than the study drug) during the study.
17. Subjects who self-report excessive consumption of xanthine-containing products (coffee, tea, cola) (i.e. > 500 mg per day of caffeine, or approximately 4 cups of coffee per day).
18. Subjects who self-report consumption of xanthine-containing products (coffee, tea, cola) or grapefruit or quinine-containing products within 48 hours before dosing through to completion of the study (Day 6).
19. Subjects who have made any blood donation within 56 days of randomization.
20. Subjects who have made any plasma donation within 7 days of randomization.
21. Subjects with a history, or suspicion, of inability to comply fully with all procedural aspects of this study.
22. Subjects with cognitive impairment preventing informed consent or cooperation during the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients undergoing moderate or severe classic essential tremor
MedDRA version: 9.1 Level: LLT Classification code 10032297 Term: Other nervous system complications

Intervention(s)

Trade Name: Xyrem 500 mg/ml oral solution
Product Name: Xyrem 500 mg/mL oral solution
Pharmaceutical Form: Oral solution
Other descriptive name: Sodium Oxybate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - To determine the efficacy and PD of single, escalating doses of sodium oxybate in subjects with ET
- To determine the PK and PD of multiple doses designed to simulate sustained delivery of sodium oxybate
- To assess the safety and tolerability of sodium oxybate using single- and multiple-dose regimens

Main Objective: To determine the relationship between drug plasma levels and safety, tolerability, and efficacy in subjects with moderate to severe essential tremor after single and multiple doses of sodium oxybate.

Primary end point(s): 1. Pharmacokinetics parameters for Xyrem
2. safety parameters
3. Pharmacodynamic parameters (Rating scales to evaluate Tremor, sedation, cognition and global impression of change; writing test on a Digital Writing Pad)

Secondary ID(s)

06-015