A 2-Part Trial of CVL-751 in Subjects With Parkinson's Disease

NCT04295642 | Completed Phase 1 FDA Drug

• 1 other identifier: CVL-751-PD-005
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This trial will be a 2-part, adaptive, open label, single and/or multiple oral dose, safety, tolerability, food effect trial of CVL-751 in subjects with Parkinson's disease. Part 1 is a placebo-controlled, single dose cohort intended for assessment of safety and tolerability. In case of intolerable AEs, Part 2 would proceed as a multiple dose titration trial to achieve a 15 mg once daily dose while maintaining L-Dopa treatment (Part 2A). In case of a favorable tolerability profile in Part 1, Part 2B would proceed as a single dose trial (similar to Part 1), with discontinuation of L-Dopa for 24 hours (12 hours pre-Day 1 dose and 12 hours post-Day 1 dose).

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (7)

• Single Dose: Peak Plasma Concentration

  Peak Plasma Concentration (Cmax) for CVL-751 and its metabolite (PF-06752844) under fasted and fed conditions

  Day 1 to 12

• Single Dose:Area under the plasma concentration-time curve

  Area under the plasma concentration-time curve (AUC) for CVL-751 and its metabolite (PF-06752844) under fasted and fed conditions

  Day 1 to 12

• Single Dose: Area under the plasma concentration-time curve from time zero to infinity

  Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-751 and its metabolite (PF-06752844) under fasted and fed conditions

  Day 1 to 12

• Single Dose: Time to Maximum Concentration

  Time to Maximum Concentration (Tmax) for CVL-751 and its metabolite (PF-06752844) under fasted and fed conditions

  Day 1 to 12

• Multiple Dose: Peak Plasma Concentration

  Peak Plasma Concentration (Cmax) for CVL-751 and its metabolite (PF-06752844) under fasted and fed conditions

  Day 16 to 29

• Multiple Dose: Area under the plasma concentration-time curve

  Area under the plasma concentration-time curve (AUCτ) for CVL-751 and its metabolite (PF-06752844) under fasted and fed conditions

  Day 16 to 29

• Multiple Dose: Time to Maximum Concentration

  Time to Maximum Concentration (Tmax) for CVL-751 and its metabolite (PF-06752844) under fasted and fed conditions

  Day 16 to 29

Secondary Outcomes (5)

• Secondary Outcome (AE) Number of subjects with reported Treatment Emergent Adverse Events (TEAEs)

  up to Day 35

• Secondary Outcome (Labs) Number of subjects with clinically significant changes in laboratory measures

  up to Day 35

• Secondary Outcome (ECGs)Number of subjects with Clinically significant changes in Electrocardiogram

  up to Day 35

• Secondary Outcome (Vital Signs) Number of subjects with Clinically meaningful changes in Vital signs

  up to Day 35

• Secondary Outcome (C-SSRS) - Change from baseline of the Columbia-Suicide Severity Rating Scale(C-SSRS)

  up to Day 35

Study Arms (2)

Part 1

PLACEBO COMPARATOR

Will include 4 subjects (3 active + 1 placebo) that will receive a single 15mg dose with approximately 48 hours of confinement and a follow-up after 7 days.

Drug: CVL-751

Part 2

EXPERIMENTAL

2A: will include 14 subjects to complete 12 with 28 days of dosing with 7 days (+/-2) of follow-up, with at least 14 days of confinement. -or- 2B: will include 20 subjects to complete 12 with 2 dosing days and 5 days of washout with 7 days (+/-2) of follow-up, with 4 days of confinement (may be increased up to 12 days at the investigators discretion).

Drug: CVL-751

Interventions

CVL-751 DRUG

Oral tablet

Part 1; Part 2

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects, ages 45 to 75 years, inclusive, at the time of signing the informed consent form (ICF).
• Body mass index (BMI) of 17.5 to 38.0 kg/m2 and a total body weight \>50 kg (110 lbs).
• Subjects with a diagnosis of that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria, with bradykinesia and motor asymmetry.
• Must be modified Hoehn \& Yahr (HY) Stage I - III inclusive.
• Must be on a stable dose of L-Dopa of at least 300 mg daily in conjunction with a dopa-decarboxylase inhibitor (eg, L-Dopa/carbidopa or L-Dopa/benserazide) administered at least 3 times per day but no more than 6 times per day for at least 2 weeks prior to the Day 1 Visit. Must be willing and able to refrain from L-Dopa treatment (in Part 1 and Part 2B) as outlined in the schedule of assessments.
• A female subject of childbearing potential (see Section 10.4, Appendix 4) who is sexually active with a nonsterilized male partner or male subject with a pregnant or a nonpregnant partner of childbearing potential must agree to use an acceptable or a highly effective method of contraception (see Section 10.4, Appendix 4) from signing of informed consent throughout the duration of the trial and for 7 days post last dose.
• Capable of giving signed informed consent as described in Section 10.1.3 (Appendix 1), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.
• Capable of consuming the standard high-fat meal.

You may not qualify if:

• Any significant Axis I psychiatric disease as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (American Psychiatric Association).
• In the opinion of the investigator (or caregiver, as applicable), has signs/symptoms suggestive of clinically significant cognitive impairment that would interfere with the ability to comply with trial procedures.
• Subjects with a Montreal Cognitive Assessment score \<26.
• History or clinical features consistent with an atypical parkinsonian syndrome (eg, ataxia, dystonia, clinically significant orthostatic hypotension).
• Has a history of psychotic symptoms requiring treatment with an antipsychotic medication within the 12 months prior to signing ICF.
• Subjects with epilepsy, or history of epilepsy, or conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), or who have increased risk of seizures as evidenced by history of electroencephalogram with epileptiform activity.
• Subjects with a history of febrile seizures only are allowed. Subjects with a history of head trauma with loss of consciousness requiring overnight hospitalization will be excluded as well.
• Subjects with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological disease that, in the opinion of the investigator or medical monitor, could compromise either subject safety or the results of the trial.
• Medical conditions that are minor or well-controlled may be considered acceptable if the condition does not expose the subject to an undue risk of a significant AE or interfere with the assessments of safety or efficacy during the course of the trial. The medical monitor should be contacted in any instance where the investigator is uncertain regarding the stability of a subject's medical conditions(s) and the potential impact of the condition(s) on trial participation.
• History of substance or alcohol-use disorder (excluding nicotine; Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria) within 2 years prior to signing the ICF.
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males \[1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor\] within 6 months prior to signing ICF.
• If a current smoker, is unable to comply with the following guidelines: agrees not to smoke on the mornings of trial dosing days and for the entire trial dosing day until completion of all trial assessments for that day.
• Subjects who answer "Yes" on the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this C-SSRS Item 5 occurred within the last 6 months OR Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR Subjects who, in the opinion of the investigator, present a serious risk of suicide.
• Subjects who have attempted suicide in the past.
• Human immunodeficiency virus seropositive status or acquired immunodeficiency syndrome, acute or chronic hepatitis B or C, with HbsAg, or hepatitis C virus antibodies at screening.

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (2)

CNS Network

Long Beach, California, 90806, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Related Publications (7)

• Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. 1967. Neurology. 2001 Nov;57(10 Suppl 3):S11-26. No abstract available.

  PMID: 11775596 BACKGROUND

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.

  PMID: 22193671 BACKGROUND

• Nussbaum RL, Ellis CE. Alzheimer's disease and Parkinson's disease. N Engl J Med. 2003 Apr 3;348(14):1356-64. doi: 10.1056/NEJM2003ra020003. No abstract available.

  PMID: 12672864 RESULT

• Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE. A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. N Engl J Med. 2000 May 18;342(20):1484-91. doi: 10.1056/NEJM200005183422004.

  PMID: 10816186 RESULT

• Schrag A, Banks P. Time of loss of employment in Parkinson's disease. Mov Disord. 2006 Nov;21(11):1839-43. doi: 10.1002/mds.21030.

  PMID: 16941456 RESULT

• Yamamoto M, Schapira AH. Dopamine agonists in Parkinson's disease. Expert Rev Neurother. 2008 Apr;8(4):671-7. doi: 10.1586/14737175.8.4.671.

  PMID: 18416667 RESULT

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Matthew Leoni, MD

  Cerevel Therapeutics, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2020
• First Posted: March 4, 2020
• Study Start: January 8, 2020
• Primary Completion: July 23, 2021
• Study Completion: July 23, 2021
• Last Updated: August 31, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)