Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study)

Adamas Pharmaceuticals

Status and phase: Completed; Phase 3; Phase 2

Conditions: Parkinson's Disease; Levodopa Induced Dyskinesia; Dyskinesia

Treatments: Drug: ADS-5102 (extended release amantadine HCl)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01397422

ADS-PAR-AM201

Details and patient eligibility

About

This is a multi-center, randomized, double-blind, placebo-controlled, 4-arm parallel group study to evaluate the tolerability and efficacy of each of three dose levels of ADS-5102 oral capsules, an extended release formulation of amantadine, dosed once daily for the treatment of levodopa-induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) higher amantadine plasma concentrations during daytime hours when dyskinesia as well as motor and non-motor symptoms of PD are most problematic, ii) low amantadine plasma concentrations overnight, which may reduce the sleep disturbances and vivid dreams occasionally associated with amantadine, and iii) a reduced initial rate of rise in plasma concentration, which is expected to improve overall tolerability of amantadine.

Enrollment: 83 patients

Sex: All

Ages: 30 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed a current IRB/IEC-approved informed consent form
• Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria
• On a stable regimen of antiparkinson's medications , including any levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation
• Experiencing troublesome dyskinesia following levodopa dosing (peak dose dyskinesia)
• Able to understand and complete a standardized PD home diary, following training

Exclusion criteria

• History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation)
• History of seizures or stroke/TIA within 2 years of screening
• History of cancer within 5 years of screening, except adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer
• Estimated GFR < 50 mL/min/1.73m2
• Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening
• If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose
• If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least 4 weeks after the completion of study treatment
• Treatment with an investigational drug or device within 30 days prior to screening
• Treatment with an investigational biologic within 6 months prior to screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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83 participants in 4 patient groups, including a placebo group

Treatment A

Placebo Comparator group

Treatment:

Drug: ADS-5102 (extended release amantadine HCl)

Treatment B

Active Comparator group

Description:

Low dose ADS-5102 (amantadine extended release)

Treatment:

Drug: ADS-5102 (extended release amantadine HCl)

Treatment C

Active Comparator group

Description:

A mid-dose ADS-5102 (amantadine extended release)

Treatment:

Drug: ADS-5102 (extended release amantadine HCl)

Treatment D

Active Comparator group

Description:

High dose ADS-5102 (amantadine extended release)

Treatment:

Drug: ADS-5102 (extended release amantadine HCl)