Motor Disorder, Parkinson Disease
Conditions
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.
Interventions
DRUGBTRX-246040
oral capsule
DRUGPlacebo
oral capsule matching BTRX-246040 capsule
Sponsors
BlackThorn Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind study
Intervention model description
The study consists of 3 sequential, single ascending dose cohorts of 8 participants each with a 6:2 randomization to BTRX-246040 or placebo
Eligibility
Sex/Gender
ALL
Age
30 Years to 76 Years
Healthy volunteers
No
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 * Male participants agree to use a reliable method of birth control during the study and for at least 90 days following the last dose of BTRX-246040 or placebo * Informed and given ample time and opportunity to think about his/her participation in this study and has given his/her written informed consent on an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved consent form * Judged to be reliable and able to keep all appointments for clinic visits, tests, and procedures, including venipuncture, and examinations required by the protocol
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 * Current major depressive episode or a Beck Depression Inventory-II (BDI-II) score above 19. Participants receiving treatment for depression with antidepressants may be enrolled if they have been on a stable daily dose for at least 8 weeks before the Screening Visit and are clinically stable in the opinion of the Principal Investigator * Currently or within 8 weeks of screening receiving bupropion * Exposure to neuroleptics (antipsychotic drugs) for more than 1 month within the past 2 years, or any exposure within the past year * Any malignancy in the 5 years prior to randomization (excluding successfully treated basal cell carcinoma of the skin or cervical carcinoma in situ) * Current or previous diagnosis of malignant melanoma or the presence of any suspicious skin lesion based on physical exam findings * Any other clinically significant medical condition or circumstance prior to randomization that, in the opinion of the Investigator, could affect participant safety, preclude evaluation of response, interfere with the ability to comply with study procedures, or prohibit completion of the study (e.g., uncontrolled diabetes mellitus, renal or hepatic impairment, coronary artery disease, evidence of significant active cardiac, respiratory, or hematologic disease, cancer with \< 5 year remission (excluding successfully treated basal cell carcinoma of the skin or cervical carcinoma in situ), chronic pain, fibromyalgia or gastric bypass) * Prior seizures (other than childhood febrile seizure) or other condition that would place the participant at increased risk of seizures or is taking anticonvulsants for seizure control * History of serious head injury (e.g., skull fracture, cerebral contusion, or trauma resulting in prolonged unconsciousness), intracranial neoplasm or hemorrhage * Orthostatic hypotension that is symptomatic or requires medication * Participation in another study of an investigational medicinal product (IMP) or medical device currently or in the last 30 days or within 5 half-lives of the IMP (whichever is longer) prior to Screening * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥ 2x upper limit of normal (ULN) or glomerular filtration rate ≤ 60 mL/min at Visit 1 (screening) * Nephritic syndrome, end-stage renal disease (and using renal replacement therapy such as hemodialysis or peritoneal dialysis), or a serum creatinine ≥ 2 mg/dL (≥ 172 μmol/L) at the Screening Visit * Any other clinically significant abnormalities (i.e., laboratory deviations requiring acute medical intervention or further medical evaluation) in laboratory results at screening including clinical chemistries, hematology, and urinalysis, that, in the judgment of the Investigator, should preclude a participant's participation at study entry * Electrocardiogram (ECG) abnormalities at Visit 1 (screening) or Visit 2 that, in the judgment of the Investigator, are clinically significant related to the participant's participation * Using the following concomitant medications (contact the Sponsor-designated medical monitor to determine eligibility when in doubt): 1. proton pump inhibitors within 5 half-lives of Screening 2. fluoxetine and irreversible monoamine oxidase inhibitors within 4 weeks of Screening * Currently taking or have taken, within 5 half-lives of Screening, any medications or supplements that are strong inhibitors or inducers of CYP3A4 * A known hypersensitivity to gelatin capsules * Investigator site personnel directly affiliated with this study, and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted * Employees of the Sponsor or of any third-party organizations involved in study who require exclusion of their employees * Have participated in a clinical trial or any other type of medical research judged by the Investigator to be scientifically or medically incompatible with this study within 30 days prior to Visit 1 (screening) * Previous completion or withdrawal from this study or any other study investigating BTRX-246040 (previously called LY2940094)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Change in UPDRS Part III From Predose to Postdose on Day 1 | 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of ON Time on Day 1 | From dose to 8 hours post-dose on Day 1 | ON is the typical functional state when patients are receiving medication and have a good response. OFF is the typical functional state when patients have a poor response in spite of taking medications. |
| Percentage of Participants Who Turned ON on Day 1 | From dose to 8 hours post-dose on Day 1 | ON is the typical functional state when patients are receiving medication and have a good response. OFF is the typical functional state when patients have a poor response in spite of taking medications. |
| Time to ON on Day 1 | From dose to 8 hours post-dose on Day 1 | ON is the typical functional state when patients are receiving medication and have a good response. OFF is the typical functional state when patients have a poor response in spite of taking medications. |
| 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 | 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). UDPRS Part III was assessed pre-dose and every 30 minutes for 4 hours and then hourly for another 4 hours (i.e., 8 hours following study drug administration) 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 | 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). An additional single item to rate dyskinesia was added to the UDPRS and was rated from 0 (no dyskinesia) to 4 (severe dyskinesia: maximal amplitude and present during most of the examinations). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BTRX-246040 Cohort 1 BTRX-246040 40 mg administered orally | 6 |
| BTRX-246040 Cohort 2 BTRX-246040 80 mg administered orally | 6 |
| BTRX-246040 Cohort 3 BTRX-246040 120 mg administered orally | 6 |
| Placebo Placebo administered orally at the same number of capsules as active drug in each Cohort | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | BTRX-246040 Cohort 1 | BTRX-246040 Cohort 2 | BTRX-246040 Cohort 3 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Customized Age | 62.3 years STANDARD_DEVIATION 7.09 | 60.5 years STANDARD_DEVIATION 8.07 | 63.5 years STANDARD_DEVIATION 4.76 | 66.3 years STANDARD_DEVIATION 5.35 | 63.15 years STANDARD_DEVIATION 6.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 6 Participants | 6 Participants | 5 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 23 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 4 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 2 / 6 | 3 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Maximal Change in UPDRS Part III From Predose to Postdose 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.
Time frame: From pre-dose to 8 hours post-dose on Day 1
Population: Modified Intent to Treat (mITT): all randomized participants who received at least 1 dose of the investigational product and had at least 1 post-baseline scoring of motor activity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 Cohort 1 | Maximal Change in UPDRS Part III From Predose to Postdose on Day 1 | -22.0 score on a scale | Standard Deviation 7.01 |
| BTRX-246040 Cohort 2 | Maximal Change in UPDRS Part III From Predose to Postdose on Day 1 | -12.5 score on a scale | Standard Deviation 4.68 |
| BTRX-246040 Cohort 3 | Maximal Change in UPDRS Part III From Predose to Postdose on Day 1 | -11.2 score on a scale | Standard Deviation 3.92 |
| Combined BTRX-246040 | Maximal Change in UPDRS Part III From Predose to Postdose on Day 1 | -15.2 score on a scale | Standard Deviation 7.08 |
| Placebo | Maximal Change in UPDRS Part III From Predose to Postdose on Day 1 | -17.0 score on a scale | Standard Deviation 12.07 |
Secondary
Area Under the Curve for UPDRS Part III During the 8 Hours of Assessment on Day 1
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). UDPRS Part III was assessed pre-dose and every 30 minutes for 4 hours and then hourly for another 4 hours (i.e., 8 hours following study drug administration) on Day 1.
Time frame: From pre-dose to 8 hours post-dose on Day 1
Population: Modified Intent to Treat (mITT): all randomized participants who received at least 1 dose of the investigational product and had at least 1 post-baseline scoring of motor activity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 Cohort 1 | Area Under the Curve for UPDRS Part III During the 8 Hours of Assessment on Day 1 | 20224.50 score on a scale*minutes | Standard Deviation 2301.418 |
| BTRX-246040 Cohort 2 | Area Under the Curve for UPDRS Part III During the 8 Hours of Assessment on Day 1 | 15464.33 score on a scale*minutes | Standard Deviation 5214.729 |
| BTRX-246040 Cohort 3 | Area Under the Curve for UPDRS Part III During the 8 Hours of Assessment on Day 1 | 11682.42 score on a scale*minutes | Standard Deviation 2231.434 |
| Combined BTRX-246040 | Area Under the Curve for UPDRS Part III During the 8 Hours of Assessment on Day 1 | 15790.42 score on a scale*minutes | Standard Deviation 4894.202 |
| Placebo | Area Under the Curve for UPDRS Part III During the 8 Hours of Assessment on Day 1 | 17547.08 score on a scale*minutes | Standard Deviation 3110.784 |
Secondary
Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment)
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). An additional single item to rate dyskinesia was added to the UDPRS and was rated from 0 (no dyskinesia) to 4 (severe dyskinesia: maximal amplitude and present during most of the examinations).
Time frame: From pre-dose to 8 hours post-dose on Day 1
Population: Modified Intent to Treat (mITT): all randomized participants who received at least 1 dose of the investigational product and had at least 1 post-baseline scoring of motor activity.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 6 hours postdose | 0.3 score on a scale | Standard Deviation 0.82 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 8 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 7 hours postdose | 0.3 score on a scale | Standard Deviation 0.82 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 120 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 90 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 60 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 240 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 210 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 180 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 5 hours postdose | 0.3 score on a scale | Standard Deviation 0.82 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 150 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 1 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 30 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 6 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 5 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 7 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 210 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 90 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 8 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 60 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 150 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 120 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 180 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 30 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 2 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 240 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 90 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 30 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 180 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 240 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 5 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 6 hours postdose | 0.3 score on a scale | Standard Deviation 0.52 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 7 hours postdose | 0.2 score on a scale | Standard Deviation 0.41 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 8 hours postdose | 0.2 score on a scale | Standard Deviation 0.41 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 60 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 120 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 150 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| BTRX-246040 Cohort 3 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 210 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 210 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 120 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 8 hours postdose | 0.1 score on a scale | Standard Deviation 0.24 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 180 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 6 hours postdose | 0.2 score on a scale | Standard Deviation 0.55 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 150 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 30 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 7 hours postdose | 0.2 score on a scale | Standard Deviation 0.51 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 90 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 60 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 240 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Combined BTRX-246040 | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 5 hours postdose | 0.1 score on a scale | Standard Deviation 0.47 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 30 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 5 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 120 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 240 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 150 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 8 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 210 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 180 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 6 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 90 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 60 minutes postdose | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Pre-dose Dyskinesia Rating (From the UPDRS Part III Motor Response and Dyskinesia Assessment) | Postdose Day 1 Change, 7 hours postdose | 0.0 score on a scale | Standard Deviation 0 |
Secondary
Duration of ON Time on Day 1
ON is the typical functional state when patients are receiving medication and have a good response. OFF is the typical functional state when patients have a poor response in spite of taking medications.
Time frame: From dose to 8 hours post-dose on Day 1
Population: Modified Intent to Treat (mITT): all randomized participants who received at least 1 dose of the investigational product and had at least 1 post-baseline scoring of motor activity. 21 participants reached an ON status on Day 1; however, only 12 participants had a time recorded for when they reached OFF status on Day 1. Therefore, Duration of ON Time on Day 1 is only available for 12 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 Cohort 1 | Duration of ON Time on Day 1 | 2.983 hours | Standard Deviation 1.8144 |
| BTRX-246040 Cohort 2 | Duration of ON Time on Day 1 | 3.750 hours | Standard Deviation 1.8484 |
| BTRX-246040 Cohort 3 | Duration of ON Time on Day 1 | 4.000 hours | — |
| Combined BTRX-246040 | Duration of ON Time on Day 1 | 3.494 hours | Standard Deviation 1.6095 |
| Placebo | Duration of ON Time on Day 1 | 4.250 hours | Standard Deviation 1.5 |
Secondary
Percentage of Participants Who Turned ON on Day 1
ON is the typical functional state when patients are receiving medication and have a good response. OFF is the typical functional state when patients have a poor response in spite of taking medications.
Time frame: From dose to 8 hours post-dose on Day 1
Population: Modified Intent to Treat (mITT): all randomized participants who received at least 1 dose of the investigational product and had at least 1 post-baseline scoring of motor activity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BTRX-246040 Cohort 1 | Percentage of Participants Who Turned ON on Day 1 | 6 Participants |
| BTRX-246040 Cohort 2 | Percentage of Participants Who Turned ON on Day 1 | 6 Participants |
| BTRX-246040 Cohort 3 | Percentage of Participants Who Turned ON on Day 1 | 4 Participants |
| Combined BTRX-246040 | Percentage of Participants Who Turned ON on Day 1 | 16 Participants |
| Placebo | Percentage of Participants Who Turned ON on Day 1 | 5 Participants |
Secondary
Time to ON on Day 1
ON is the typical functional state when patients are receiving medication and have a good response. OFF is the typical functional state when patients have a poor response in spite of taking medications.
Time frame: From dose to 8 hours post-dose on Day 1
Population: Modified Intent to Treat (mITT): all randomized participants who received at least 1 dose of the investigational product and had at least 1 post-baseline scoring of motor activity. 21 participants reached an ON status on Day 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 Cohort 1 | Time to ON on Day 1 | 3.575 hours | Standard Deviation 2.7749 |
| BTRX-246040 Cohort 2 | Time to ON on Day 1 | 2.583 hours | Standard Deviation 2.7462 |
| BTRX-246040 Cohort 3 | Time to ON on Day 1 | 3.646 hours | Standard Deviation 2.7742 |
| Combined BTRX-246040 | Time to ON on Day 1 | 3.221 hours | Standard Deviation 2.6231 |
| Placebo | Time to ON on Day 1 | 3.200 hours | Standard Deviation 2.8417 |