Nabilone for Non-motor Symptoms in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Nabilone 0.25 mg; Placebo
Intervention description: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis; capsule, corn starch, daily basis
Intervention MeSH terms: Nabilone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: placebo-controlled, double-blind, parallel-group with 1 : 1 randomization
Enrollment: 48.0
Sex: All
Minimum age: 30 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Parkinson´s Disease; cannabinoids; non-motor symptoms

Summary:

      This is a randomized placebo-controlled, double-blind, parallel-group, enriched enrollment
      randomized withdrawal study assessing the efficacy and safety of nabilone for non-motor
      symptoms in patients with Parkinson´s Disease. Nabilone is an analogue of
      tetrahydrocannabinol (THC), the psychoactive component of cannabis. Nabilone acts as a
      partial agonist on both Cannabinoid 1 (CB1) and Cannabinoid 2 (CB2) receptor in humans and
      therefore mimics the effect of THC but with more predictable side effects and less euphoria.

      Part 1 is an open-label dose adjustment phase of the study. In eligible patients, a screening
      period is followed by an open-label nabilone dose optimization phase and a stable phase for
      at least 1 week. Treatment responders will be included in Part 2 of the study (randomized
      placebo-controlled, double-blind, parallel-grouped).

      Part 2 is the placebo-controlled, double-blind, parallel-group randomized withdrawal phase of
      the study.
    

Eligibility criteria:

        Inclusion Criteria:

        In order to be eligible for the study subjects must meet all inclusion criteria:

          1. Age ≥30 years

          2. Diagnosis of Parkinson´s Disease (PD): PD should be either de novo or on stable
             medication without disturbing motor fluctuations or dyskinesia.

          3. NMS with a score of ≥4 on MDS-UPDRS Part 1. One of the following domains have to be
             affected with a score ≥2: 1.4 (anxious mood) or 1.9 (pain)

          4. On a stable regimen of anti-parkinson medications for at least 30 days prior to
             screening and willing to continue the same doses and regimens during study
             participation

          5. Any other current and allowed prescription/non-prescription medications and/or
             nutritional supplements taken regularly must have been at a stable dose and regimen
             for at least 30 days prior to screening, and subject must be willing to continue the
             same doses and regimens during study participation

          6. Patient is informed and had enough time and opportunity to think about his/her
             participation in the study and has signed a current Institutional Review
             Board-approved informed consent form

          7. Contraception

               1. Women of childbearing potential must use or attest an acceptable method* of
                  contraception starting 4 weeks prior to study drug administration and for a
                  minimum of 1 month after study completion.

               2. Men with a potentially fertile partner must be willing to use an acceptable
                  method of contraception for the duration of the study and for 3 months after
                  study drug discontinuation or have had a vasectomy.

        Exclusion Criteria:

        Patients with any of the following characteristics will be excluded from entering the
        study:

          1. Patient previously participated in any study with nabilone.

          2. Current use of cannabinoids or use of cannabinoids within 30 days prior to screening.

          3. Patient is currently participating in or has participated in another study of
             investigational products within 30 days prior to screening.

          4. Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post
             stroke).

          5. Patient presents with motor complications which are, based on the investigator's
             judgment, not adequately controlled (i.e. a score ≥2 on one of the items of the
             MDS-UPDRS Part IV at screening)

          6. Hoehn and Yahr stage > 3

          7. Evidence of disturbing (i.e. requiring treatment) impulse control disorder in the
             participant. Can be resolved through a structural interview during screening period.

          8. History of neurosurgical intervention for PD

          9. presence of symptomatic orthostatic hypotension at screening (MDS-UPDRS 1.12 > 2)

         10. Use of prohibited medication (e.g. benzodiazepines (except for clonazepam up to a
             maximum of 1.5 mg per d), lithium, opioids, buspirone, muscle relaxing agents, central
             nervous system depressing substances, ...)

         11. Patients with laboratory values that are out-of-range at Screening (or within 4 weeks
             prior to Screening) and haven´t been reviewed and documented as not clinically
             significant by the investigator. Lab Tests can be repeated for confirmation.

         12. Patients with known or newly diagnosed sinus tachycardia in ECG evaluation at
             Screening or within 4 weeks prior to Screening.

         13. presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive
             Disorder, psychosis) or symptom (e.g., hallucinations, agitation, paranoia) (MDS-UPDRS
             1.2 and/or 1.3 > 2)

         14. Patients who had a recent suicidal attempt (active, interrupted, aborted) within the
             past five years or report suicidal ideation within the past 6 months.

         15. presence of dementia (MDS-UPDRS 1.1 > 2, Mini-Mental State Examination of <24 at the
             Screening visit)

         16. clinically significant or unstable medical or surgical condition at Screening or
             Baseline visit that may preclude safety and the completion of the study participation
             (based on the investigator's judgment).

         17. Patients with moderate or severe hepatic or renal impairment.

         18. Patient has a history of chronic alcohol or drug abuse within the last 2 years.

         19. women of child-bearing potential who do not practice an acceptable method of birth
             control

         20. Pregnant women or women planning to become pregnant during the course of the study and
             nursing women.

         21. Patients who are knowingly hypersensitive to any of the components of the
             investigational medicinal product or excipients.

         22. Patient is legally incapacitated or persons held in an institution by legal or
             official order

         23. Persons with any kind of dependency on the investigator or employed by the Sponsor or
             investigator