Phase 2A, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BTRX-246040 in Parkinson's Disease Subjects With Motor Fluctuations
Overview
- Phase
- Phase 2
- Intervention
- BTRX-246040
- Conditions
- Parkinson Disease
- Sponsor
- BlackThorn Therapeutics, Inc.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Maximal Change in UPDRS Part III From Predose to Postdose on Day 1
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and efficacy of BTRX-246040 in participants with Parkinson's Disease who have motor fluctuations and predictable early morning off periods.
Detailed Description
Study treatment is 1 day and total duration of the study is up to 36 days, including an approximate 28-day screening period. The study consists of 3 sequential, ascending dose cohorts of 8 participants each with a 6:2 randomization to BTRX-246040 or placebo. The planned dosing for each cohort is 40, 80, and 120 mg. After enrollment of the first cohort is completed, doses for subsequent cohorts may be modified based on review of the available data (safety, tolerability, efficacy, and pharmacokinetics) by an unblinded Dosing Review Committee (DRC). A similar review and determination of dosing for the subsequent cohort is to be performed after completion of each cohort and based on all data available from previous cohorts. Participants who meet entry criteria assessed at the screening visit (up to 28 days prior to Day 1) present to the clinic on the morning of Day 1 (treatment day) in the practically defined OFF state (having withheld anti-parkinsonian medications after 10:00 PM the evening prior). Participants are to be dosed with study drug and remain on site for an 8-hour observation period with Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor response, dyskinesia rating and ON/OFF status assessed pre-dose, every 30 minutes for 4 hours post-dose, and then hourly for 4 additional post-dose hours (i.e., 8 hours total post-dose) prior to being discharged. Blood for pharmacokinetics are to be collected 6 times at scheduled intervals within the 8-hour observation period. A follow-up safety visit is scheduled 7 days later.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosed with Parkinson's disease (PD), consistent with the United Kingdom PD Society Brain Bank Criteria for the Diagnosis of PD
- •Men or women ≥ 30 years old and ≤ 76 years old
- •Female participants must be either surgically sterilized or 2 years post menopausal at screening
- •Modified Hoehn and Yahr Staging ≤ 3 in the ON state
- •Montreal Cognitive Assessment (MoCA) Score ≥ 26
- •Currently has a clear and decisive response to levodopa, and receiving a stable dose of levodopa (at least 4 doses per day of levodopa or ≥ 3 doses per day of RytaryTM (carbidopa and levodopa) extended-release capsules for at least 4 weeks prior to screening)
- •Experiencing motor fluctuations during waking hours with at least 2 hours of OFF periods each day, including predictable early morning OFF periods, based on participant assessment
- •Able to participate in the study in the practically defined OFF state
- •All anti-parkinsonian medications maintained at a stable dose for at least 4 weeks prior to the initial Screening Visit with the exception of monoamine oxidase B (MAO-B) inhibitors, which must be maintained at a stable level for at least 8 weeks prior to the screening visit
- •Approved by a central Enrollment Authorization Committee as meeting entry criteria and being a suitable candidate for the study
Exclusion Criteria
- •Diagnosis of secondary or an atypical Parkinsonian syndrome
- •Severe disabling dyskinesia
- •Clinically significant psychosis or hallucinations or history of psychosis in past 6 months
- •History of previous neurosurgery for PD
- •Currently or previously on Duopa/Duodopa
- •Currently taking apomorphine
- •Has a diagnosis or history of a substance related disorder per Diagnostic and Statistical Manual of Mental Disorders V edition (DSM-V) criteria (including alcohol but excluding nicotine and caffeine), during the 12 months prior to the Screening Visit
- •Medical or recreational use of marijuana in the 6 months prior to the Screening Visit
- •Has tested positive at the Screening Visit for drugs of abuse (opiates, cannabinoids, methadone, cocaine, and amphetamines \[including ecstasy\])
- •Active suicidal ideation within 1 year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia- Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 1 year
Arms & Interventions
BTRX-246040 Cohort 1
BTRX-246040 40 mg administered orally
Intervention: BTRX-246040
BTRX-246040 Cohort 2
BTRX-246040 80 mg administered orally
Intervention: BTRX-246040
BTRX-246040 Cohort 3
BTRX-246040 120 mg administered orally
Intervention: BTRX-246040
Placebo Cohorts 1-3
Placebo is administered orally at the same number of capsules as active drug in each Cohort. Placebo capsules consist of inactive ingredients and look identical to BTRX-246040.
Intervention: Placebo
Outcomes
Primary Outcomes
Maximal Change in UPDRS Part III From Predose to Postdose on Day 1
Time Frame: From pre-dose to 8 hours post-dose on Day 1
UPDRS = Unified Parkinson's Disease Rating Scale. The Unified Parkinson's Disease Rating Scale (UPDRS) Part III is a 14-item rating scale, which consists of the motor examination. Each item is scored from 0 (Normal) to 4 (Most severe). The score ranges from 0-56.
Secondary Outcomes
- Duration of ON Time on Day 1(From dose to 8 hours post-dose on Day 1)
- Percentage of Participants Who Turned ON on Day 1(From dose to 8 hours post-dose on Day 1)
- Time to ON on Day 1(From dose to 8 hours post-dose on Day 1)
- Area Under the Curve for UPDRS Part III During the 8 Hours of Assessment on Day 1(From pre-dose to 8 hours post-dose on Day 1)
- Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment)(From pre-dose to 8 hours post-dose on Day 1)