An Active-Controlled Extension Study to NCT01155466 [P04938] and NCT01227265 [P07037] (P06153)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 3

Conditions: Idiopathic Parkinson Disease; Parkinson Disease

Treatments: Drug: Placebo to preladenant; Drug: Rasagiline; Drug: Placebo to rasagiline; Drug: Preladenant

Study type: Interventional

Funder types: Industry

Identifiers

NCT01215227

P06153

2009-015162-57 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 839 patients

Sex: All

Ages: 30 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants who have completed the 12-week treatment period of the parent trial, P04938 or P07037.
• Participants must be willing and able to provide written informed consent for P06153.
• 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
• An elevation from baseline BP in the parent study (P04938 or P07037) of systolic BP >= 40 mm Hg or diastolic BP ≥ 20 mm Hg.
• A participant must not have a history within the past 5 years of a primary or recurrent malignant disease with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with a normal prostate-specific antigen (PSA) post resection.
• Any participant with an average daily consumption of more than three 4-ounce glasses (118 mL) of wine or the equivalent.
• A participant must not have received certain prespecified medications or ingested high tyramine-containing aged cheeses (e.g., Stilton) for a prespecified time window before the trial, during the trial, and for 2 weeks after the trial.
• Any participant with allergy/sensitivity to the investigational products or their excipients.
• Any female participant breast feeding or considering breast feeding.
• Any female participant pregnant or intending to become pregnant.
• Any participant with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial.
• Any participant with a member or a family member of the personnel of the investigational or sponsor staff directly involved with this trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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839 participants in 6 patient groups

Preladenant 2 mg

Experimental group

Description:

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.

Treatment:

Drug: Preladenant

Drug: Placebo to rasagiline

Preladenant 5 mg

Experimental group

Description:

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.

Treatment:

Drug: Preladenant

Drug: Placebo to rasagiline

Preladenant 5 mg (on placebo in parent study)

Experimental group

Description:

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.

Treatment:

Drug: Preladenant

Drug: Placebo to rasagiline

Preladenant 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Preladenant

Rasagiline 1 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to preladenant

Drug: Rasagiline

Rasagiline 1 mg (on placebo in parent study)

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to preladenant

Drug: Rasagiline