A Randomized Double Blind Placebo Controlled Proof of Concept Study to Evaluate Safety, Tolerability and Efficacy of Daily Oral THX-110 in Treating Adults With Tourette Syndrome ("Entourage")
试验速览
- 阶段
- 2 期
- 发起方
- SciSparc
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Change in YGTSS-TTS
研究概览
简要总结
This study evaluates the efficacy and safety of THX-110 in the management of tics and other symptoms (e.g. rage attacks, anxiety, depression, sleep difficulties) in patients with Tourette syndrome. In the first part of the study, half of the patients will receive THX-110, while the other half will receive a placebo. After completion of the first study part, patients will have the opportunity to continue into the second part of the study. In this part, all participants will receive THX-110.
详细描述
THX-110 is an investigational drug and is being developed for the treatment of patients with Tourette syndrome and other conditions. THX-110 consists of an active substance from cannabis (dronabinol, tetrahydrocannabinol, THC) and PEA, a substance that occurs naturally in the human body, in animals and plants.
Dronabinol and similar active substances are already approved in some countries for the treatment of other conditions. In some countries, various cannabis-based medications are currently being used in the treatment of patients with Tourette syndrome, mostly without official approval.
PEA has already been used and well tolerated in numerous clinical trials. The combination of PEA and dronabinol is assumed to show better efficacy compared to treatment with dronabinol alone.
The planned study will evaluate the efficacy of THX-110 in the management of tics and other symptoms in patients with Tourette syndrome. Other objectives are to assess study drug dosage and to identify side effects that may be associated with the study drug.
In the first part of the study, half of the patients will receive THX-110, while the other half will receive a placebo. The treatment phase will last 12 weeks. After completion of the first part, patients can decide if they want to participate in the second part of the study. In this optional second part of the study, all patients will receive THX-110 for 12 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Tourette syndrome according to DSM-5
- •Male and female subjects with an age between ≥18 and <65 years
- •Total tic score (TTS) of the YGTSS >18
- •Medication (and stimulation parameters for deep brain stimulation) for tics and comorbidities must be on a stable dose for at least 6 weeks before entering the study and subject must consent to maintain the stable dose during the study
- •Signed written informed consent and willingness to comply with treatment and follow-up procedures
- •Subjects capable of understanding the investigational nature, potential risks and benefits of the clinical study
- •Women of child-bearing potential must have a negative pregnancy test (i.e., negative for urine human chorionic gonadotropin [hCG]) before first treatment with study medication. They must practice a highly effective, reliable and medically approved contraceptive regimen during the study (e.g., theoretical failure rate less than 1% per year a when used consistently and correctly), which include oral or parenteral or implanted hormonal contraception, vaginal ring releasing hormonal contraception (e.g., Nuvaring), intrauterine device or intrauterine system. Post-menopausal women may enter this study. Post-menopausal women are defined as those without menses in the past 12 months without an alternative medical cause, and with a serum follicle stimulating hormone (FSH) in the post-menopausal range. Women who are surgically sterile may enter this study with historical documentation of surgical procedure (bilateral tubal ligation or bilateral oophorectomy at least 6 weeks prior screening or hysterectomy or uterine agenesis) and a negative pregnancy test.
- •Male subjects must be willing to use a condom with sexual partners during this study and for a period of three months following the last administration of study medication until the follow-up visit. Male subjects must be willing to abstain from sperm donation for 3 months after the completion of this study.
排除标准
- •Comorbid OCD, ADHD, depression, or anxiety disorder when unstable and/or in need of an initial adjustment for a therapy
- •Presence of a comorbid psychiatric condition as developmental disability, psychotic illness or bipolar disorder
- •Ongoing behavioural treatment for tics
- •History of schizophrenia, seizure, psychotic, severe personality, or pervasive developmental disorder
- •Current clinical diagnosis of substance abuse or dependence
- •History of cannabis dependence
- •Secondary and other chronic tic disorders or other significant neurological disorders
- •History of severe cardiac diseases, severe cardiovascular diseases, severe renal disorders, or severe hepatic diseases and/or positive for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B
- •Concomitant medications have to be on stable dose since at least 6 weeks before entering the study and must be well tolerated at baseline without causing dizziness, confusion, sedation, or somnolence such as central nervous system depressants (e.g., barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, scopolamine, antihistamines, tricyclic antidepressants, other anticholinergic agents, muscle relaxants)
- •Use of cannabis or CBM in the 30-day period prior to study entry and/or positive delta-9-THC urine test at baseline
- •Positive pregnancy test, i.e., positive for urine beta-hCG
- •Pregnant or breast-feeding women
- •Subjects who received any investigational medication or used any investigational device within 30 days prior to the first dose of study medication or is actively participating in any investigational drug or device study, or is scheduled to receive an investigational drug or to use an investigational device during the course of the study
- •Subjects with a known allergy, hypersensitivity, or intolerance to the active substances and/or excipients of study medication (e.g., cannabis, cannabinoids, sesame oil)
- •Any condition, which in the opinion of the investigator, would interfere with the evaluation of the study product or poses a health risk to the subject
- •Subjects who are employees of the sponsor or employees or close relatives of the investigator
研究组 & 干预措施
THX-110 (dronabinol plus PEA)
Double-blind phase and extension open label phase:
Dose range of 2.5 mg to 10 mg dronabinol (1 to 4 capsules) plus 800 mg PEA (2 tablets) taken orally once daily; starting dose is 2.5 mg dronabinol plus 800 mg PEA. Up-titration is performed within maximal 3 weeks. The titration phase is followed by a maintenance phase of 9 weeks at stable dose.
干预措施: THX-110 (dronabinol plus PEA) (Drug)
Placebo
Double-blind phase:
Range of 1 to 4 dronabinol placebo capsules plus 2 PEA placebo tablets taken orally once daily; starting dose is 1 dronabinol placebo capsule plus 2 PEA placebo tablets. Up-titration is performed within maximal 3 weeks. The titration phase is followed by a maintenance phase of 9 weeks at stable dose.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in YGTSS-TTS
时间窗: Baseline and week 12 of the double-blind phase
Absolute change in YGTSS-TTS as a continuous endpoint at week 12 of the double-blind phase (visit 9) compared to baseline.
次要结局
- Pre-monitory Urge for Tics Scale (PUTS)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Yale-Brown Obsessive Compulsive Scale (Y BOCS)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Clinical Global Impression-Improvement Score (CGI-I)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Beck Depression Inventory (BDI)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- YGTSS-GS (= YGTSS-TTS + YGTSS-impairment score)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- YGTSS-TTS as a binary responder criterion and as a continuous endpoint at week 7 of the double-blind phase(Baseline and week 7 of the double-blind phase)
- Tourette Syndrome-Quality of Life Scale (GTS-QoL)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Beck Anxiety Inventory (BAI)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Modified Rush Video-Based Tic Rating Scale (MRVS)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Clinical Global Impression-Severity Score (CGI-S)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Pittsburgh Sleep Quality Index (PSQI)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- 12-item short-form (SF-12) Health Survey(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Rage Attacks Questionnaire (RAQ)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Response to treatment according to YGTSS-TTS(Baseline and week 12 of the double-blind phase)
- Adult Tic Questionnaire (ATQ)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)
- Conners' Adult ADHD Rating Scale (CAARS)(Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase)