Trial Outcomes & Findings for Safety and Efficacy of AVP-923 in the Treatment of Levodopa-induced Dyskinesia in Parkinson's Disease Patients (NCT NCT01767129)

Last Updated: 2022-04-29

Results Overview

The MDS-UDysRS was developed to evaluate involuntary movements often associated with treated Parkinson's disease (PD). Levodopa-Induced Dyskinesia severity was assessed via video analysis by unbiased blinded central raters, and was calculated using the Intensity Scale from Part 3 of the MDS-UDysRS. The Intensity Scale was made up of seven body parts: face, neck, right arm/shoulder, left arm/shoulder, trunk, right leg/hip, and left leg/hip. Each body part was scored on a variety of disability items (communication, drinking, and ambulation \[walking\]) on a scale of 0 (normal) to 4 (incapacitating dyskinesia) with a maximum total score of 28. For each body part, the highest disability score was summed to calculate the intensity score. A score of '0' was assigned to questions associated with the dressing task which were not performed due to the placement of the treatment infusion (IV) line. A higher score indicated more severe symptoms.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)

Results posted on

2022-04-29

Participant Flow

Participant milestones

Participant milestones
Measure	AVP-923-45; Placebo In Treatment Period 1, participants received one AVP-923-45 (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. In Treatment Period 2, participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. The two treatment periods were separated by a 14-day washout period.	Placebo; AVP-923-45 In Treatment Period 1, participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. In Treatment Period 2, participants received one AVP-923-45 capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. The two treatment periods were separated by a 14-day washout period.
Treatment Period 1 (14 Days) STARTED	7	7
Treatment Period 1 (14 Days) COMPLETED	6	7
Treatment Period 1 (14 Days) NOT COMPLETED	1	0
Treatment Period 2 (14 Days) STARTED	6	7
Treatment Period 2 (14 Days) COMPLETED	6	7
Treatment Period 2 (14 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	AVP-923-45; Placebo In Treatment Period 1, participants received one AVP-923-45 (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. In Treatment Period 2, participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. The two treatment periods were separated by a 14-day washout period.	Placebo; AVP-923-45 In Treatment Period 1, participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. In Treatment Period 2, participants received one AVP-923-45 capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days. The two treatment periods were separated by a 14-day washout period.
Treatment Period 1 (14 Days) Adverse Event	1	0

Baseline Characteristics

Safety and Efficacy of AVP-923 in the Treatment of Levodopa-induced Dyskinesia in Parkinson's Disease Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=14 Participants Participants were randomized to receive AVP-923-45 (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) and placebo in one of two treatment sequences: AVP-923-45 in Treatment Period 1, placebo in Treatment Period 2; or placebo in Treatment Period 1, AVP-923-45 in Treatment Period 2. The two treatment periods were separated by a 14-day washout period. In both treatment periods, participants received either one AVP-923-45 capsule or one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days.
Age, Continuous	64.1 years STANDARD_DEVIATION 7.32 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race/Ethnicity, Customized White	13 Participants n=5 Participants
Race/Ethnicity, Customized Indian Sub-Continent	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)

Population: Efficacy Evaluable (EE) Population: all randomized participants who completed the study

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Least Squares Mean Dyskinesia Severity Area Under the Curve (AUC) Score As Assessed By Modified Movement Disorder Society-Unified Dyskinesia Rating Scale (MDS-UDysRS) Part 3	966.0 (Score on a scale)*hour Standard Error 42.22	1049.4 (Score on a scale)*hour Standard Error 42.22

SECONDARY outcome

Timeframe: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)

Population: EE Population

The MDS-UDysRS was developed to evaluate involuntary movements often associated with treated PD. Part 4 of the MDS-UDysRS objectively measures the disability associated with levodopa-induced dyskinesia. Disability was assessed via video analysis by unbiased blinded central raters. Disability was evaluated for communication, drinking from a cup, and ambulation items. Each item was rated from 0 (no dyskinesia) to 4 (most severe disability), with a sum range of 0 to 12. A score of '0' was assigned to questions associated with the dressing task because it was not performed due to placement of the IV line. A higher score indicated more severe symptoms.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Least Squares Mean Disability Area Under the Curve (AUC) Score As Assessed By Modified Movement Disorder Society-Unified Dyskinesia Rating Scale (MDS-UDysRS) Part 4	409.4 (Score on a scale)*hour Standard Error 14.87	428.3 (Score on a scale)*hour Standard Error 14.87

SECONDARY outcome

Timeframe: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)

Population: EE Population

The Modified MDS-UPDRS (4 parts) was used to assess the severity of parkinsonian disability. Part III of the MDS-UPDRS was used as an objective measure of the severity of parkinsonian disability per motor examination with focus on the treated side tremor and motor fluctuations. The motor examination were videotaped using a standardized protocol for review by an expert central rater blinded to the treatment schedule. A total of 11 items were scored as follows: 0 (normal), 1 (slight), 2 (mild), 3 (moderate), 4 (severe), with a maximum total score of 44. For each part, a higher score indicated more severe symptoms. Due to placement of the IV line, a score of '0' was assigned to rigidity questions.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Least Squares Mean Motor Movement Area Under the Curve Score As Assessed by Modified Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III	6568.9 (Score on a scale)*hour Standard Error 383.26	6397.0 (Score on a scale)*hour Standard Error 383.26

SECONDARY outcome

Timeframe: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)

Population: EE Population

Timed finger tapping test was used to quantify the upper extremity impairment in participants with idiopathic PD. Timed finger tapping was assessed using the Objective Parkinson's Disease Measurement (OPDM) System. Participants were instructed to tap for 60 seconds while speed and accuracy were assessed across 4 tests; right and left two finger test (m,n keystrokes) and one finger test (p,q keystrokes). The mean peak finger tapping score was calculated using the individual peak values. A higher score signifies improvement (faster typing, more accuracy), while a lower score signifies increased symptom severity.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Least Squares Mean Timed Finger Tapping Area Under the Curve (AUC) Score	820.9 (Score on a scale)*hour Standard Error 40.80	772.1 (Score on a scale)*hour Standard Error 40.80

SECONDARY outcome

Timeframe: Baseline (Day 1); Post-Baseline (Day 14 or 42)

Population: EE Population

The MDS-UPDRS was used to assess the status of PD. Parts I and II (completed by the participant) and Part IV (completed by a rater) of the MDS-UPDRS provided a subjective measure of parkinsonian disability. Part I measured non-motor experiences of daily living, Part II measured motor experiences of daily living, and Part IV measures motor complications associated with PD. Each part was comprised of a series of questions, and each question was scored from 0 (normal) to 4 (severe). Part I and Part II were each comprised of 13 items; the total score ranges from 0 (normal) to 52 (severe). Part III was comprised of 33 items; the total score ranges from 0 (normal) to 132 (severe). Part IV was comprised of 6 items; the total score ranged from 0 (normal) to 24 (severe). For each part, a higher score indicated more severe symptoms. Post-Baseline was Visit 2 (Day 14) or Visit 4 (Day 42). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Change From Baseline in MDS-UPDRS Scores for Part I, II, and IV Part I	-1.2 score on a scale Standard Error 0.43	-0.1 score on a scale Standard Error 0.43
Change From Baseline in MDS-UPDRS Scores for Part I, II, and IV Part IV	-2.9 score on a scale Standard Error 0.84	-0.5 score on a scale Standard Error 0.84
Change From Baseline in MDS-UPDRS Scores for Part I, II, and IV Part II	-0.0 score on a scale Standard Error 0.92	-0.2 score on a scale Standard Error 0.92

SECONDARY outcome

Timeframe: Baseline (Day 1); Post-Baseline (Day 14 or 42)

Population: EE Population

The MDS-UDysRS was developed to evaluate involuntary movements often associated with treated PD. Part 1 (On-Dyskinesia \['jerking or twisting movements that occur when your medicine is working'\]) and Part 2 (Off-Dyskinesia \["spasms or cramps that can be painful and occur when your PD medications are not taken or are not working\]) of the MDS-UDysRS were assessed by a blinded rater. Parts 1B and 2B (participant questionnaires) were completed at home by the participant. Part 1 comprised of 11 items, and Part 2 comprised of 4 items. All items were assigned a score of: 0, normal; 1, slight; 2, mild; 3, moderate; 4, severe. The total score for Parts 1 and 2 ranged from 0 to 44 and from 0 to 16, respectively. Higher scores indicate increased symptom severity. Post-Baseline was Visit 2 (Day 14) or Visit 4 (Day 42). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Change From Baseline in MDS-UDysRS Scores for Part 1 and 2 Part 1	-3.9 score on a scale Standard Error 1.34	0.00 score on a scale Standard Error 1.34
Change From Baseline in MDS-UDysRS Scores for Part 1 and 2 Part 2	-0.7 score on a scale Standard Error 0.77	0.6 score on a scale Standard Error 0.77

SECONDARY outcome

Timeframe: Baseline; Post-Baseline (Days 14 and 42)

Population: EE Population

The PD motor diary is a home diary used to assess functional status in participants with PD with motor fluctuations and dyskinesia. Participants were instructed to complete the PD motor diary at home for a minimum of 3 consecutive days within the 7 days prior to Visits 2 and 4 (Days 14 and 42). Baseline is Visit 1 (Day 1) or Visit 3 (Day 29); Post-Baseline is Visit 2 (Day 14) or Visit 4 (Day 42). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Change From Baseline in PD Motor Diary Ratings Of Duration Of "On-time Without Bothersome Dyskinesia"	0.5 hours Standard Error 1.01	0.5 hours Standard Error 0.93

SECONDARY outcome

Timeframe: Baseline; Post-Baseline (Day 14 or 42)

Population: EE Population

The PDQ-39 was a self-reported questionnaire consisting of 39 questions assessing Parkinson's disease-specific health quality of life covering 8 aspects of quality of life: mobility; activities of daily living; emotional wellbeing; stigma; social support; cognitive impairment (cognitions); communication; bodily discomfort. Each item was scored on 5-point scale: 0 = Never (better in outcome), 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (worse in outcome). Total scores ranged between 0 to 156. Higher scores indicated poor quality of life. Baseline was Visit 1 (Day 1) or Visit 3 (Day 29); Post-Baseline was Visit 2 (Day 14) or Visit 4 (Day 42). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Mobility	0.2 score on a scale Standard Error 2.45	2.0 score on a scale Standard Error 2.69
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Activities of Daily Living	-4.6 score on a scale Standard Error 2.14	3.9 score on a scale Standard Error 2.14
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Emotional Well Being	-4.5 score on a scale Standard Error 2.90	2.9 score on a scale Standard Error 2.90
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Stigma	-3.7 score on a scale Standard Error 4.10	0.3 score on a scale Standard Error 4.10
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Social support	-6.0 score on a scale Standard Error 3.60	3.8 score on a scale Standard Error 3.60
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Cognitive impairment (Cognitions)	-4.1 score on a scale Standard Error 3.64	0.2 score on a scale Standard Error 3.64
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Communication	-3.7 score on a scale Standard Error 2.43	2.4 score on a scale Standard Error 2.43
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period Bodily discomfort	-7.4 score on a scale Standard Error 4.60	-2.2 score on a scale Standard Error 4.60

SECONDARY outcome

Timeframe: Baseline; Post-Baseline (Day 14 or 42)

Population: EE Population

The PDQ-39 was the most widely used PD-specific measure of health status. It consists of 39 questions, covering 8 aspects of quality of life: mobility; activities of daily living; emotional wellbeing; stigma; social support; cognitive impairment (cognitions); communication; bodily discomfort. The instrument was developed on the basis of interviews with people diagnosed with PD. The PDQ-39-SI) score was calculated as the weighted addition of scores on all 8 dimensions of the PDQ-39. The total score ranged from 0 (no disease impact) to 100 (severe disease impact). Baseline was Visit 1 (Day 1) or Visit 3 (Day 29); Post-Baseline was Visit 2 (Day 14) or Visit 4 (Day 42). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Change From Baseline in PDQ-39 Single Index (PDQ-39-SI) Scores at the End of Each Treatment Period	-4.2 score on a scale Standard Error 1.60	2.2 score on a scale Standard Error 1.76

SECONDARY outcome

Timeframe: Screening (Day -28); End of each treatment period (Days 14 or 42)

Population: EE Population

The MoCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total score is calculated by summing the items from each domain. Total scores can range from 0 to 30; lower scores indicate cognitive dysfunction. A final total score of 26 and above is considered normal. Change from Screening was calculated as the post-Screening value minus the Screening value.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Change From Screening in the Montreal Cognitive Assessment (MoCA) Calculated Score at the End of Each Treatment Period	0.1 score on a scale Standard Error 0.27	0.6 score on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Baseline; Post-Baseline (Days 14 and 42)

Population: EE Population

The PGIC was a 7-point scale used to assess treatment response as judged by the participant. The participant was asked to assess change in dyskinesia symptoms and change in overall PD symptoms (e.g., slowness, stiffness, balance) on a score range of 1, much improved; 2, improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, worse; 7, much worse. The average PGIC score was calculated at each visit by treatment group. Baseline is Visit 1 (Day 1) or Visit 3 (Day 29); Post-Baseline is Visit 2 (Day 14) or Visit 4 (Day 42). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	AVP-923-45 n=13 Participants Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 Participants Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Change From Baseline in the Dyskinesia and Other PD Symptoms Score As Assessed by Patient Global Impression of Change (PGIC) Dyskinesia	2.7 score on a scale Standard Error 0.35	3.7 score on a scale Standard Error 0.35
Change From Baseline in the Dyskinesia and Other PD Symptoms Score As Assessed by Patient Global Impression of Change (PGIC) Other PD symptoms	4.2 score on a scale Standard Error 0.26	4.1 score on a scale Standard Error 0.26

Adverse Events

AVP-923-45

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Avanir Medical Information

Avanir Pharmaceuticals

Phone: 855-572-2722

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	AVP-923-45 n=14 participants at risk Participants received one AVP-923-45 capsule (45 milligrams \[mg\] dextromethorphan hydrobromide \[DM\]/10 mg quinidine sulfate \[Q\]) once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.	Placebo n=13 participants at risk Participants received one placebo capsule once daily in the morning for 3 days, then twice daily, approximately 12 hours apart, for 11 days in either Treatment Period 1 or Treatment Period 2. The two treatment periods were separated by a 14-day washout period.
Cardiac disorders Palpitations	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Ear and labyrinth disorders Tinnitus	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	14.3% 2/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	7.7% 1/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Flatulence	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Paraesthesia oral	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
General disorders Asthenia	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
General disorders Fatigue	21.4% 3/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Upper respiratory tract infection	0.00% 0/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	7.7% 1/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Fall	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Wrist fracture	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Balance disorder	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	14.3% 2/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Dysgeusia	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Dyskinesia	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Freezing phenomenon	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Parkinsonism	14.3% 2/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Somnolence	21.4% 3/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Tremor	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Psychiatric disorders Insomnia	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Reproductive system and breast disorders Male sexual dysfunction	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/13 • up to Day 42 TEAEs, defined as events that began on or after the first dose of study drug up until 30 days after the last dose, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.