Efficacy, Safety and Tolerability Study of APL-130277 for the Acute Treatment of OFF Episodes in Patients With Parkinson's Disease

The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The least square mean change in the MDS-UPDRS Part III score from pre-dose to 30 minutes post-dose at MV4 is presented. A negative change from pre-dose indicates an improvement.

Time frame: At t=0 (just prior to dosing) and t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The modified Intention-To-Treat (mITT) Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

During the CGI-I assessment the clinician using the question Compared to his/her condition on baseline, how much has he/she changed? provided 1 of the following responses: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse and 7 = very much worse. The percentage of patients who improved at MV4 (responses 1 - 3) are presented.

Time frame: At MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The mean change in the MDS-UPDRS Part III score from pre-dose to 15 minutes post-dose at MV4 is presented. A negative change indicates an improvement.

Time frame: At t=0 (just prior to dosing) and t=15 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

The PDQ-39 was self-administered by the patient during screening and at each MV. The PDQ-39 assessed the impact of PD on the quality of life in the preceding month using 39-items, each anchored with 5 responses: Never, Occasionally, Sometimes, Often and Always. Items were grouped into 8 scales (Mobility, Activities of daily living, Emotional well-being, Stigma, Social support, Cognitions, Communication and Bodily discomfort) that were scored by expressing summed item scores as a percentage score ranging between 0 and 100. The PDQ-39 summary index score was derived by the sum of the 8 PDQ-39 scale scores divided by 8, yielding a score between 0 and 100. 0 indicates perfect health and 100 indicates worse health as assessed by the measure. A negative change indicates an improvement.

Time frame: At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

Part II of the MDS-UPDRS assessed motor experiences of daily living and was self-administered by the patient. The MDS-UPDRS Part II score was calculated as the sum of the individual items of the MDS-UPDRS Part II questionnaire (items 2.1 - 2.13), and was based on 13-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 52, with a lower score indicating better motor function for daily living and a higher score indicating more severe motor symptoms. The mean change in the MDS-UPDRS Part II score from the screening visit to Week 12 of the Maintenance Treatment Phase is presented. A negative change indicates an improvement.

Time frame: At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

Patients self-administered their doses of randomized study medication in order to treat up to 5 'OFF' episodes per day and recorded the time of self-administration and the 'ON'/'OFF' status at 30 minutes post-dose in a home dosing diary. A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. The percentage of instances in which a full 'ON' response was achieved at 30 minutes out of all recorded episodes was calculated and is presented, and the mean percentage is presented.

Time frame: 2 days prior to MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

During the PGI-I assessment the patient was asked to answer the question Since starting study medication, how has your illness changed? with 1 of the following responses: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse and 7 = very much worse. The percentage of patients who improved at MV4 (gave responses 1 - 3) are presented.

Time frame: At MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. Patients were asked if they attained a full 'ON' state anytime within 30 minutes of dosing. The predicted response rates are presented and were estimated using a generalized linear mixed model.

Time frame: At t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. The percentage of patients who attained a full 'ON' within 30 minutes of dosing, and whose duration from time when study medication began to have an effect lasted for at least 30 minutes were evaluated. The predicted response rates are presented and were estimated using a generalized linear mixed model.

Time frame: At MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.

The time to effect at MV4 was described using the Kaplan-Meier method, including an estimate of the median time to effect and corresponding 95% confidence interval.

Time frame: At MV4 (Week 12 of the Maintenance Treatment Phase).

Population: The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented.