A Phase 3, 40-Week, Active-Controlled, Double-Blind, Double-Dummy Extension Study of Preladenant in Subjects With Moderate to Severe Parkinson's Disease (Phase 3, Protocol No. P06153)
Overview
- Phase
- Phase 3
- Intervention
- Preladenant
- Conditions
- Parkinson Disease
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 839
- Primary Endpoint
- Percentage of Participants With Suicidality
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
The primary purpose of this extension study is to assess the long-term safety and tolerability of preladenant in participants from parent studies NCT01155466 [P04938] and NCT01227265 [P07037] with moderate to severe Parkinson's Disease (PD). The study will also characterize the long-term efficacy of preladenant in participants with PD.
Participants will continue to receive their stable regimen of levodopa (L-dopa) plus any adjunct medications during the study as prescribed by their physician. Several classes of adjunct medications may be used, including Amantadine, anticholinergics, dopa decarboxylase inhibitors, and dopamine agonists.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who have completed the 12-week treatment period of the parent trial, P04938 or P
- •Participants must be willing and able to provide written informed consent for P
- •Participants must be able to adhere to dose and visit schedules.
- •Participants must be taking L-dopa.
- •Participants may be taking additional adjunct PD medications (e.g., dopamine agonists, entacapone).
- •Each participant must have results of clinical laboratory tests (hematology, blood chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator as evidenced by the last available test results from the parent study (P04938 or P07037), and no results fall within the parameters for exclusion described below in the exclusion criterion for liver-related findings.
- •There has been no change in, or there has been no finding to warrant checking, serology status (for cytomegalovirus \[CMV\], Epstein-Barr virus \[EBV\], and Hepatitis B, C, and E).
- •Each participant must have results of a physical examination within normal limits, including blood pressure, within normal limits or clinically acceptable limits to the investigator, and not within the parameters for exclusion described below in the exclusion criterion for blood pressure.
- •All participants who are sexually active or plan to be sexually active agree to use a highly effective method of birth control while the participant is in the study and for 2 weeks after the last dose of study drug. A male participant must not donate sperm within 2 weeks after the last dose of study drug.
Exclusion Criteria
- •Any participant who discontinued from P04938 or P07037 for any reason.
- •Any participant with a severe or ongoing unstable medical condition (e.g., any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, seizures, or alcohol/drug dependence).
- •Any participant with a history of poorly controlled diabetes (e.g., hemoglobin A1c \> 8.5) or significantly abnormal renal function (e.g., creatinine \> 2.0 mg/dL) in the opinion of the investigator.
- •As a continuation of the liver-related withdrawal criteria from the parent studies (P04938 and P07037), any participant with elevated values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin (T BIL), as evidenced by the most recent chemistry panel results in the parent study, meeting any one of the following criteria:
- •ALT or AST \> 8 x upper limit of normal (ULN).
- •ALT or AST \> 5 x ULN for more than 2 weeks.
- •ALT or AST \> 3 x ULN and (T-BIL \> 2 x ULN or international normalized ratio \[INR\] \> 1.5 that is not due to anti-coagulation) at the same visit.
- •ALT or AST \> 3 x ULN with the appearance of worsening fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (\> 5%).
- •As a continuation of the blood pressure (BP) withdrawal criteria from the parent study (P04938 or P07037), any participant meeting the following criteria for the second of two consecutive visits separated by 7 days (i.e., the participant met one of the BP criteria once already, 7 days before the P06153 screening visit):
- •Systolic BP ≥ 180 mm Hg or diastolic BP ≥ 105 mm Hg, or
Arms & Interventions
Preladenant 2 mg
Participants who received preladenant 2 mg in parent study NCT01155466 or NCT01227265 will continue to receive preladenant 2 mg in this extension study. Participants will receive preladenant 2 mg taken orally twice daily (BID): one tablet plus placebo capsule to rasagiline in the morning, and one tablet in the evening, for 40 weeks.
Intervention: Preladenant
Preladenant 2 mg
Participants who received preladenant 2 mg in parent study NCT01155466 or NCT01227265 will continue to receive preladenant 2 mg in this extension study. Participants will receive preladenant 2 mg taken orally twice daily (BID): one tablet plus placebo capsule to rasagiline in the morning, and one tablet in the evening, for 40 weeks.
Intervention: Placebo to rasagiline
Preladenant 5 mg
Participants who received preladenant 5 mg in parent study NCT01155466 or NCT01227265 will continue to receive preladenant 5 mg in this extension study. Participants will receive preladenant 5 mg taken orally BID: one tablet plus placebo capsule to rasagiline in the morning, and one tablet in the evening, for 40 weeks.
Intervention: Preladenant
Preladenant 5 mg
Participants who received preladenant 5 mg in parent study NCT01155466 or NCT01227265 will continue to receive preladenant 5 mg in this extension study. Participants will receive preladenant 5 mg taken orally BID: one tablet plus placebo capsule to rasagiline in the morning, and one tablet in the evening, for 40 weeks.
Intervention: Placebo to rasagiline
Preladenant 5 mg (on placebo in parent study)
Participants who received placebo to preladenant tablet in parent study NCT01155466 or NCT01227265 will receive preladenant 5 mg in this extension study. Participants will receive preladenant 5 mg taken orally BID: one tablet plus placebo capsule to rasagiline in the morning, and one tablet in the evening, for 40 weeks.
Intervention: Preladenant
Preladenant 5 mg (on placebo in parent study)
Participants who received placebo to preladenant tablet in parent study NCT01155466 or NCT01227265 will receive preladenant 5 mg in this extension study. Participants will receive preladenant 5 mg taken orally BID: one tablet plus placebo capsule to rasagiline in the morning, and one tablet in the evening, for 40 weeks.
Intervention: Placebo to rasagiline
Preladenant 10 mg
Participants who received preladenant 10 mg in parent study NCT01155466 or NCT01227265 will continue to receive preladenant 10 mg in this extension study. Participants will receive preladenant 10 mg taken orally BID: one tablet plus placebo capsule to rasagiline in the morning, and one tablet in the evening, for 40 weeks.
Intervention: Preladenant
Rasagiline 1 mg
Participants who received rasagiline 1 mg in parent study NCT01155466 or NCT01227265 will continue to receive rasagiline 1 mg in this extension study. Participants will receive rasagiline 1 mg capsule once a day: one capsule plus placebo tablet to preladenant in the morning, and one placebo tablet to preladenant in the evening, for 40 weeks.
Intervention: Rasagiline
Rasagiline 1 mg
Participants who received rasagiline 1 mg in parent study NCT01155466 or NCT01227265 will continue to receive rasagiline 1 mg in this extension study. Participants will receive rasagiline 1 mg capsule once a day: one capsule plus placebo tablet to preladenant in the morning, and one placebo tablet to preladenant in the evening, for 40 weeks.
Intervention: Placebo to preladenant
Rasagiline 1 mg (on placebo in parent study)
Participants who received placebo to rasagiline capsule in parent study NCT01155466 or NCT01227265 will receive rasagiline 1 mg in this extension study. Participants will receive rasagiline 1 mg capsule once a day: one capsule plus placebo tablet to preladenant in the morning, and one placebo tablet to preladenant in the evening, for 40 weeks.
Intervention: Rasagiline
Rasagiline 1 mg (on placebo in parent study)
Participants who received placebo to rasagiline capsule in parent study NCT01155466 or NCT01227265 will receive rasagiline 1 mg in this extension study. Participants will receive rasagiline 1 mg capsule once a day: one capsule plus placebo tablet to preladenant in the morning, and one placebo tablet to preladenant in the evening, for 40 weeks.
Intervention: Placebo to preladenant
Outcomes
Primary Outcomes
Percentage of Participants With Suicidality
Time Frame: Up to 42 weeks
The number of participants with suicidality using the Columbia - Suicide Severity Rating Scale (C-SSRS) was reported. The C-SSR was used in this study only for the purpose of safety monitoring by measuring the incidence of different types of suicidality categories during treatment. The assessment was done by the nature of the responses, not by a numbered scale. Participants who reported at least one occurrence of suicidal behavior or suicidal ideation were counted as having experienced suicidality. Suicidal behavior included suicide attempt, aborted attempt, interrupted attempt, or preparatory behavior. Suicidal ideation included a wish to die or active suicidal thought with or without method, intent or plan.
Percentage Change From Baseline in Total Epworth Sleepiness Scale (ESS) Score at Week 40
Time Frame: Baseline and Week 40
The ESS is a self-administered questionnaire providing a measure of a person's general level of daytime sleepiness, or their average sleep propensity in daily life. The scale consists of 8 situations in which the participant rates their tendency to become sleepy on a scale of 0=no chance of dozing to 3=high chance of dozing. The overall score is the sum of the scores for the 8 situations for a minimum of 0 and a maximum of 24 with a higher score indicating greater sleepiness.
Percentage of Participants With Diastolic Blood Pressure ≥105 mmHg
Time Frame: Up to 42 weeks
The percentage of participants with Diastolic Blood Pressure ≥105 mmHg was reported. On Day 1 and Early Termination, blood pressure was measured as follows: Participant lay supine for 5 minutes, then had blood pressure taken; then stood for 3 minutes and had blood pressure taken; then rested for 10 minutes, at which time the process was repeated twice (ie, three rounds total). For all other blood pressure measurements, the procedure needed only to be done once (ie, one round).
Percentage of Participants With Aspartate Aminotransferase (AST) ≥3 Times Upper Limit of Normal and ≥10% Increase From Baseline
Time Frame: Up to 42 weeks
The number of participants with AST ≥3 times the upper limit of normal and a ≥10% increase was reported. Laboratory safety blood work was collected from participants at Week 4, Week 6, and Week 8 visits.
Percentage of Participants With Systolic Blood Pressure ≥180 mmHg
Time Frame: Up to 42 weeks
The percentage of participants with Systolic Blood Pressure ≥180 mm Hg was reported. On Day 1 and Early Termination, blood pressure was measured as follows: Participant lay supine for 5 minutes, then had blood pressure taken; then stood for 3 minutes and had blood pressure taken; then rested for 10 minutes, at which time the process was repeated twice (ie, three rounds total). For all other blood pressure measurements, the procedure needed only to be done once (ie, one round).
Percentage of Participants With Alanine Aminotransferase (ALT) ≥3 Times Upper Limit of Normal and ≥10% Increase From Baseline
Time Frame: Up to 42 weeks
The number of participants with ALT ≥3 times the upper limit of normal and a ≥10% increase was reported. Laboratory safety blood work was collected from participants at Week 4, Week 6, and Week 8 visits.