Clinical trial NCT03651726: A Study to Examine the Efficacy of a Therapeutic THX-110 for Tourette Syndrome
Official title: 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")
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Tourette Syndrome
Lead sponsor: SciSparc
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
First posted: 2018-08-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo controlled, proof of concept study, followed by an open uncontrolled treatment phase
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Tourette syndrome according to DSM-5
2. Male and female subjects with an age between ≥18 and \<65 years
3. Total tic score (TTS) of the YGTSS \>18
4. CGI-S ≥4
5. 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
6. Signed written informed consent and willingness to comply with treatment and follow-up procedures
7. Subjects capable of understanding the investigational nature, potential risks and benefits of the clinical study
8. 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.
9. 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.

Exclusion Criteria:

1. Comorbid OCD, ADHD, depression, or anxiety disorder when unstable and/or in need of an initial adjustment for a therapy
2. Presence of a comorbid psychiatric condition as developmental disability, psychotic illness or bipolar disorder
3. Ongoing behavioural treatment for tics
4. History of schizophrenia, seizure, psychotic, severe personality, or pervasive developmental disorder
5. Current clinical diagnosis of substance abuse or dependence
6. History of cannabis dependence
7. Secondary and other chronic tic disorders or other significant neurological disorders
8. 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
9. 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)
10. Use of cannabis or CBM in the 30-day period prior to study entry and/or positive delta-9-THC urine test at baseline
11. Positive pregnancy test, i.e., positive for urine beta-hCG
12. Pregnant or breast-feeding women
13. 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
14. Subjects with a known allergy, hypersensitivity, or intolerance to the active substances and/or excipients of study medication (e.g., cannabis, cannabinoids, sesame oil)
15. 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
16. Subjects who are employees of the sponsor or employees or close relatives of the investigator

Primary outcomes:
measure: Change in YGTSS-TTS
timeFrame: Baseline and week 12 of the double-blind phase
Secondary outcomes:
measure: Response to treatment according to YGTSS-TTS
timeFrame: Baseline and week 12 of the double-blind phase
measure: YGTSS-TTS as a binary responder criterion and as a continuous endpoint at week 7 of the double-blind phase
timeFrame: Baseline and week 7 of the double-blind phase
measure: YGTSS-GS (= YGTSS-TTS + YGTSS-impairment score)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Modified Rush Video-Based Tic Rating Scale (MRVS)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Clinical Global Impression-Improvement Score (CGI-I)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Clinical Global Impression-Severity Score (CGI-S)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Adult Tic Questionnaire (ATQ)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Tourette Syndrome-Quality of Life Scale (GTS-QoL)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Pre-monitory Urge for Tics Scale (PUTS)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Beck Depression Inventory (BDI)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Yale-Brown Obsessive Compulsive Scale (Y BOCS)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Conners' Adult ADHD Rating Scale (CAARS)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Beck Anxiety Inventory (BAI)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: 12-item short-form (SF-12) Health Survey
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
measure: Rage Attacks Questionnaire (RAQ)
timeFrame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie
city: Munich
country: Germany
facility: LMU Klinikum der Universität München, Klinik für Psychiatrie und Psychotherapie
Study officials:
affiliation: Medizinische Hochschule Hannover, Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie
name: Kirsten Müller-Vahl, Prof. Dr.
role: STUDY_CHAIR
References: