Advanced Parkinson's Disease
Conditions
Keywords
Levodopa-carbidopa intestinal gel, Advanced Parkinson's disease, Severe motor fluctuations, Dyskinesia
Brief summary
To explore the safety, tolerability, pharmacokinetics and efficacy of ABT-SLV187 in advanced Parkinson's disease (PD) patients with severe motor complications. The complications of medical devices for the naso-jejunum (NJ) infusion system of ABT-SLV187 will also be investigated.
Interventions
DRUGABT-SLV187
DRUGOral Levodopa/Carbidopa
Tablet; contains 100 mg levodopa and 10 mg carbidopa
DEVICEInfusion Pump: CADD-Legacy® 1400 Pump
General infusion pump, manufactured by Smiths Medical (US)
DEVICENJ-Tube: Silicon ED Tube
Device used to deliver nutrition/drug to stomach/intestine or to aspirate stomach fluid, manufactured by Create Medic Co., Ltd. (Japan)
DEVICEAdaptor: Hakko Adaptor
Accessory set for fluid infusion set, consisting of caps, connectors and adapters, etc, manufactured by Hakko Medical (Japan)
Sponsors
Abbott Japan Co.,Ltd
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Idiopathic PD according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank criteria * PD stage corresponds to 4 or 5 in the 'off' state according to the modified Hoehn & Yahr (H & Y) classification of disease severity * Levodopa-responsive subjects demonstrate some identifiable 'ON response' established by observation by Investigator and demonstrate severe motor fluctuations in spite of individually optimized treatment and where therapy options are indicated
Exclusion criteria
* Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists such as secondary parkinsonism * Undergone surgery for the treatment of PD * Contraindications to levodopa * Subjects with any neurological deficit that may interfere with the study assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | During the Run-in period (up to approximately 28 days) | AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with this treatment. SAE: an event that results in the death of a subject, is life threatening, results in hospitalization or prolongation of hospitalization, is a congenital anomaly, results in persistent or significant disability/incapacity, or other important medical event. Severity was rated as mild, moderate, or severe. AEs of special interest included: device-associated gastrointestinal disorders; cardiovascular fatalities; aspiration including aspiration pneumonia; a diagnosis of peripheral polyneuropathy (axonal, demyelinating or mixed type); possible symptoms of peripheral polyneuropathy; clinically significant weight loss. 'AEs at least possibly related' are defined as those that were assessed by investigator as probably related or possibly related. |
| Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | From NJ placement to end of ABT-SLV187 Treatment Period (Day 21) +30 days | AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with this treatment. SAE: an event that results in the death of a subject, is life threatening, results in hospitalization or prolongation of hospitalization, is a congenital anomaly, results in persistent or significant disability/incapacity, or other important medical event. Severity was rated as mild, moderate, or severe. AEs of special interest included: device-associated gastrointestinal disorders; cardiovascular fatalities; aspiration including aspiration pneumonia; a diagnosis of peripheral polyneuropathy (axonal, demyelinating or mixed type); possible symptoms of peripheral polyneuropathy; clinically significant weight loss. 'AEs at least possibly related' are defined as those that were assessed by investigator as probably related or possibly related. |
| Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | M=male, F=female, MCV=mean corpuscular volume, MCH=mean corpuscular hemoglobin, MCHC=mean corpuscular hemoglobin concentration. |
| Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | M=male, F=female, γ-GTP=gamma-glutamyl transpeptidase. |
| Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | M=male, F=female |
| Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | — |
| Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | ↓=decrease, ↑=increase, BL=baseline, temp.=temperature, SBP=systolic blood pressure, Sup.=supine, Sta.=standing, DBP=diastolic blood pressure. |
| Number of Participants With Potentially Clinically Significant 12-lead Electrocardiogram (ECG) Results During the ABT-SLV187 Treatment Period | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | High potentially clinically significant Bazett's heart rate-corrected QT interval (QTcB) values were: 450 msec for males / 470 msec for females. |
| Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the Normal State on the Treatment Response Scale (TRS) I | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | Participants were video recorded a total of 10 times for 1 to 2 minutes every 60 minutes while performing a standardized sequence of motor tasks: rest, finger taps, rapid alternating movement of hands, arising from chair and gait, including confirmation of postural stability. Based on these video recordings, a Video Evaluation Committee consisting of 3 neurologists individually evaluated the following Video Assessment and Treatment Response Scale (TRS) under blinded conditions: Finger Taps, Rapid Alternating Movement of Hands, Arising from Chair, Gait, Body Bradykinesia and Hypokinesia, Dyskinesia. The average of the neurologists' evaluations was calculated as a percentage of ratings in the Normal state (ie, mild OFF to ON with mild dyskinesia) on the TRS I (total 10 assessments per day). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse. |
| Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187 | Baseline (Day -1): pre-dose; 15, 30, 45, 60 mins post-morning dose; every 30 mins thereafter for 12 hrs. Day 21: pre-dose; 15, 30, 45, 60 mins post-infusion; every 30 mins from hrs 1 to 12 post-infusion; every 2 hrs from 12 to 16 hrs post-infusion. | Tmax of levodopa, carbidopa, and its metabolite 3-O-methyldopa (3-OMD) after administration of oral L/C tablets and intra-jejunal administration of ABT-SLV187. |
| Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | Cmax, Cavg, Cmin, and Cmin (2-12 hours) of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21). Cmin values for levodopa and carbidopa during the 16 hours of infusion were observed either at time 0 or 15 min after start of the infusion and were a result of drug washout prior to establishment of infusion. |
| Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the OFF and Dyskinesia States on the TRS I and the Normal, OFF, and Dyskinesia States on the TRS II | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | Participants were video recorded a total of 10 times for 1 to 2 minutes every 60 minutes while performing a standardized sequence of motor tasks: rest, finger taps, rapid alternating movement of hands, arising from chair and gait, including confirmation of postural stability. Based on these video recordings, a Video Evaluation Committee consisting of 3 neurologists individually evaluated the following Video Assessment and TRS under blinded conditions: Finger Taps, Rapid Alternating Movement of Hands, Arising from Chair, Gait, Body Bradykinesia and Hypokinesia, Dyskinesia for TRS I, with the addition of Tremor at Rest and Postural Stability for TRS II. The average of the 3 neurologists' evaluations was calculated as a percentage of ratings in the Normal state (ie, mild OFF to ON with mild dyskinesia), the Off state (moderate OFF to severe OFF), and the Dyskinesia state (ON with moderate dyskinesia to ON with severe dyskinesia) on the TRS I or II. |
| AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | AUC0-12/Dose0-12 of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21). AUC0-16/Dose0-16 of levodopa, carbidopa, and 3-OMD after administration of intra-jejunal administration of ABT-SLV187 (Day 21). |
| Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | Degree of Fluctuation (calculated as \[Cmax - Cmin\] / Cavg)) of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21). |
| The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | AUC0-12 and AUC0-16 of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21). |
| Change From Baseline to the End of Treatment in Parkinson's Disease Diary Assessment | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | For each half hour period during 3 consecutive days prior to each assessment of the diary, participants (and/or their caregivers) entered into a diary whether they were asleep, in the ON motor state or in the OFF motor state in the following 5 grades: asleep, OFF, ON (no dyskinesia \[D\]), ON with non-troublesome dyskinesia (NTD), ON with troublesome dyskinesia (TD). ON time is when PD symptoms are well controlled by the drug. OFF time is when PD symptoms are not adequately controlled by the drug. Dyskinetic time is time with involuntary muscle movement. The ON or OFF times were calculated as the average of 3 daily times from the diaries. w/o = without, w/ = with |
| Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Baseline (Day -1), Endpoint (Day 21) | Participants were video recorded a total of 10 times for 1 to 2 minutes every 60 minutes while performing a standardized sequence of motor tasks. Based on these video recordings, a Video Evaluation Committee consisting of 3 neurologists individually evaluated the video under blinded conditions using the following assessments: Tremor at Rest (UPDRS item #20), Finger Taps (UPDRS #23), Rapid Alternating Movement of Hands (UPDRS #25), Arising from Chair (UPDRS #27), Gait (UPDRS #29), Postural Stability (UPDRS #30), Body Bradykinesia and Hypokinesia (UPDRS #31), and Dyskinesia (evaluated with the Goetz Dyskinesia Rating Scale). The UPDRS score is the sum of the answers to individual questions, each of which are measured on a 5-point scale (0-4), with higher scores associated with more disability. The Goetz Dyskinesia Rating Scale is a 5-point scale of the severity of dyskinesias, from 0 (absent) to 4 (violent dyskinesias). |
| Ratio of Metabolite 3-OMD to Levodopa (M/P [AUC0-12]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | M/P (AUC0-12) after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21). |
| Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | — |
| Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score ranges from 0-176, with 176 representing the worst (total) disability, and 0 no disability. The Part I Score is the sum of the answers to the 4 questions related to Mentation, Behavior and Mood, and ranges from 0-16. The Part II score is the sum of the answers to the 13 questions related to Activities of Daily Living, and ranges from 0-52. The Part III score is the sum of the 27 answers related to Motor Examination, and ranges from 0-108. The Part IV Score is the sum of the answers to the 11 questions related to Complications of Therapy, and ranges from 0-23. The Part IV dyskinesia subscore ranges from 0-12. For each part of the UPDRS, higher scores are associated with more disability. |
| Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients, including Mobility, Activities of Daily Living, Emotional Well-being, Stigma, Social Support, Cognition, Communication, and Bodily Discomfort, as well as a Summary Index Total Score. Scores for each are on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. |
| Modified Hoehn and Yahr Staging at Baseline and End of Treatment | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | Participant's ON and OFF states staged according to the Modified Hoehn and Yahr criteria, an 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. ON time is when PD symptoms are well controlled by the drug. OFF time is when PD symptoms are not adequately controlled by the drug. |
| Schwab and England Activities of Daily Living Scale at Baseline and End of Treatment | Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21) | The Schwab and England scale was used to rate the subject's activities of daily living by recording the percentage score, ranging between being completely independent (100%) and totally dependent (10%). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levodopa-carbidopa Intestinal Gel Following a 28-day Run-in Period where participants are switched from prior anti-PD medications to monotherapy with an oral 100 mg levodopa/10 mg carbidopa tablet (optimized every 3rd hour during waking hours), participants receive ABT-SLV187 (levodopa-carbidopa intestinal gel), administered over 16 hours a day with an infusion pump directly into the proximal jejunum by a naso-jejunum (NJ) tube, for 3 weeks.
The individually-adjusted infusion dose (composed of the morning dose, the continuous maintenance dose, and the extra dose) is optimized by the Investigator for each participant during the study based on the participant's symptoms. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Levodopa-carbidopa Intestinal Gel |
|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 6.19 |
| Age, Customized < 65 years | 4 participants |
| Age, Customized >/= 65 years | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 4 / 6 |
| serious Total, serious adverse events | 0 / 8 | 1 / 6 |
Outcome results
Primary
Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the Normal State on the Treatment Response Scale (TRS) I
Participants were video recorded a total of 10 times for 1 to 2 minutes every 60 minutes while performing a standardized sequence of motor tasks: rest, finger taps, rapid alternating movement of hands, arising from chair and gait, including confirmation of postural stability. Based on these video recordings, a Video Evaluation Committee consisting of 3 neurologists individually evaluated the following Video Assessment and Treatment Response Scale (TRS) under blinded conditions: Finger Taps, Rapid Alternating Movement of Hands, Arising from Chair, Gait, Body Bradykinesia and Hypokinesia, Dyskinesia. The average of the neurologists' evaluations was calculated as a percentage of ratings in the Normal state (ie, mild OFF to ON with mild dyskinesia) on the TRS I (total 10 assessments per day).
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the Normal State on the Treatment Response Scale (TRS) I | 15.33 percentage of ratings | Standard Deviation 14.26 |
p-value: 0.074Paired t-test
Primary
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period
AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with this treatment. SAE: an event that results in the death of a subject, is life threatening, results in hospitalization or prolongation of hospitalization, is a congenital anomaly, results in persistent or significant disability/incapacity, or other important medical event. Severity was rated as mild, moderate, or severe. AEs of special interest included: device-associated gastrointestinal disorders; cardiovascular fatalities; aspiration including aspiration pneumonia; a diagnosis of peripheral polyneuropathy (axonal, demyelinating or mixed type); possible symptoms of peripheral polyneuropathy; clinically significant weight loss. 'AEs at least possibly related' are defined as those that were assessed by investigator as probably related or possibly related.
Time frame: During the Run-in period (up to approximately 28 days)
Population: Full safety sample: participants who had at least one dose of oral levodopa-carbidopa study drug in the Run-in Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | AE | 7 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | AE at least possibly related to study drug/device | 5 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | Severe AE | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | SAE | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | AE leading to discontinuation of study drug | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | SAE at least possibly drug or drug device-related | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | AE of special interest | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | AE caused by study drug | 5 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | AE caused by devices | NA participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | AE caused by NJ tube insertion | NA participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period | Fatal AE | 0 participants |
Primary
Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period
AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with this treatment. SAE: an event that results in the death of a subject, is life threatening, results in hospitalization or prolongation of hospitalization, is a congenital anomaly, results in persistent or significant disability/incapacity, or other important medical event. Severity was rated as mild, moderate, or severe. AEs of special interest included: device-associated gastrointestinal disorders; cardiovascular fatalities; aspiration including aspiration pneumonia; a diagnosis of peripheral polyneuropathy (axonal, demyelinating or mixed type); possible symptoms of peripheral polyneuropathy; clinically significant weight loss. 'AEs at least possibly related' are defined as those that were assessed by investigator as probably related or possibly related.
Time frame: From NJ placement to end of ABT-SLV187 Treatment Period (Day 21) +30 days
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | AE | 4 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | AE at least possibly related to study drug/device | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | Severe AE | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | SAE | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | AE leading to discontinuation of study drug | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | SAE at least possiby drug or drug device-related | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | AE of special interest | 2 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | AE caused by study drug | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | AE caused by devices | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | AE caused by NJ tube insertion | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period | Fatal AE | 0 participants |
Primary
Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period
M=male, F=female, γ-GTP=gamma-glutamyl transpeptidase.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Creatine kinase [U/L]: 57 M / 32 F | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Creatine kinase [U/L]: 197 M / 180 F | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Blood urea nitrogen [mg/dL]: 6 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Blood urea nitrogen [mg/dL]: 20 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low Creatinine [mg/dL]: 0.61 M / 0.47 F | 2 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High Creatinine [mg/dL]: 1.04 M / 0.79 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Total bilirubin [mg/dL]: 0.2 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Total bilirubin [mg/dL]: 1.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Alanine aminotransferase [U/L]: 5 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Alanine aminotransferase [U/L]: 40 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Aspartate aminotransferase [U/L]: 10 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Aspartate aminotransferase [U/L]: 40 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Alkaline phosphatase [U/L]: 115 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Alkaline phosphatase [U/L]: 359 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS γ-GTP [U/L]: 0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS γ-GTP [U/L]: 70 M / 30 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Sodium [mEq/L]: 136 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Sodium [mEq/L]: 147 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Potassium [mEq/L]: 3.6 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Potassium [mEq/L]: 5.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Calcium [mg/dL]: 8.7 | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Calcium [mg/dL]: 10.1 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Chloride [mEq/L]: 98 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Chloride [mEq/L]: 109 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Magnesium [mg/dL]: 1.8 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Magnesium [mg/dL]: 2.6 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Inorganic Phosphors [mg/dL]: 2.4 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Inorganic Phosphors [mg/dL]: 4.3 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Uric acid [mg/dL]: 3.7 M / 2.5 F | 2 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Uric acid [mg/dL]: 7 M / 7.0 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Total cholesterol [mg/dL]: 150 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Total cholesterol [mg/dL]: 219 | 2 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Total protein [g/dL]: 6.7 | 5 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Total protein [g/dL]: 8.3 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Albumin [g/dL]: 4.0 | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Albumin [g/dL]: 5.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Glucose [mg/dL]: 70 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Glucose [mg/dL]: 109 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Triglycerides [mg/dL]: 50 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Triglycerides [mg/dL]: 149 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Bicarbonate [mEq/L]: 22 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Bicarbonate [mEq/L]: 29 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | Low PCS Lactate dehydrogenase [U/L]: 115 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period | High PCS Lactate dehydrogenase [U/L]: 245 | 1 participants |
Primary
Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period
M=male, F=female
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | Low PCS Vitamin B6 pyridoxamine [ng/mL]: </= 0.6 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | Low PCS Vitamin B6 pyridoxal [ng/mL]: 6.0 M/4.0 F | 4 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | High PCS Vitamin B6 pyridoxal [ng/mL]: 40 M / 19 F | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | Low PCS Vitamin B6 pyridoxine [ng/mL]: </= 3.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | Low PCS Vitamin B12 [pg/mL]: 180 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | High PCS Vitamin B12 [pg/mL]: 914 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | Low PCS Homocysteine [nmol/mL]: 3.7 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | High PCS Homocysteine [nmol/mL]: 13.5 | 4 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period | Low PCS Folic acid [ng/mL]: < 3.1 | 1 participants |
Primary
Number of Participants With Potentially Clinically Significant 12-lead Electrocardiogram (ECG) Results During the ABT-SLV187 Treatment Period
High potentially clinically significant Bazett's heart rate-corrected QT interval (QTcB) values were: 450 msec for males / 470 msec for females.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant 12-lead Electrocardiogram (ECG) Results During the ABT-SLV187 Treatment Period | 0 participants |
Primary
Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period
M=male, F=female, MCV=mean corpuscular volume, MCH=mean corpuscular hemoglobin, MCHC=mean corpuscular hemoglobin concentration.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Hematocrit [%]: 39.8 M / 33.4 F | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Hematocrit [%]: 51.8 M / 44.9 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Hemoglobin [g/dL]: 13.5 M / 11.3 F | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Hemoglobin [g/dL]: 17.6 M / 15.2 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS RBC Count [*10^4/µL]: 427 M / 376 F | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS RBC Count [*10^4/µL]: 570 M / 500 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS WBC Count [/µL]: 3900 M / 3500 F | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS WBC Count [/µL]: 9800 M / 9100 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Neutrophils [%]: 40.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Neutrophils [%]: 74.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Lymphocytes [%]: 18.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Lymphocytes [%]: 59.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Monocytes [%]: 0.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Monocytes [%]: 8.0 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Basophils [%]: 0.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Basophils [%]: 2.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Eosinophils [%]: 0.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Eosinophils [%]: 6.0 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS Platelet count [*10^4/µL]: 13.1 M / 13.0 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS Platelet count [*10^4/µL]: 36.2 M/ 36.9 F | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS MCV [FL]: 82.7 M / 79.0 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS MCV [FL]: 101.6 M / 100.0 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS MCH [Pg]: 28 M / 26.3 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS MCH [Pg]: 34.6 M / 34.3 F | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | Low PCS MCHC [%]: 31.6 M / 30.7 F | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period | High PCS MCHC [%]: 36.6 M / 36.6 F | 0 participants |
Primary
Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period
↓=decrease, ↑=increase, BL=baseline, temp.=temperature, SBP=systolic blood pressure, Sup.=supine, Sta.=standing, DBP=diastolic blood pressure.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Low PCS Weight [kg]: ≥7% ↓ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | High PCS Weight [kg]: ≥7% ↑ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | High PCS Body temp. [⁰C]: ≥38.8 and ≥1.1 ↑ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Low PCS SBP Sup. [mmHg]: ≤90 and >30 ↓ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | High PCS SBP Sup. [mmHg]: ≥180 and >40 ↑ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Low PCS SBP Sta. [mmHg]: ≤90 and >30 ↓ from BL | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | High PCS SBP Sta. [mmHg]: ≥180 and >40 ↑ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Low PCS SBP Orthostatic [mmHg]: ↓ of ≥30 in SBP | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Low PCS DBP Sup. [mmHg]: ≤50 and >30 ↓ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | High PCS DBP Sup. [mmHg]: ≥105 and >30 ↑ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Low PCS DBP Sta. [mmHg]: ≤50 and >30 ↓ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | High PCS DBP Sta. [mmHg]: ≥105 and >30 ↑ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Low PCS DBP Orthostatic [mmHg]: ↓ of ≥20 in DBP | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Pulse rate [bpm]: ≤50 and >30 ↓ from BL | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period | Pulse rate [bpm]: ≥120 and >30 ↑ from BL | 0 participants |
Primary
Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | Low PCS Specific gravity: 1.002 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | High PCS Specific gravity: 1.030 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | Low PCS pH: 4.5 | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | High PCS pH: 8.0 | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | High PCS Protein: > trace | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | High PCS Glucose: > trace | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | High PCS Occult blood: > negative | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period | High PCS Ketone: > negative | 0 participants |
Secondary
AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187
AUC0-12/Dose0-12 of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21). AUC0-16/Dose0-16 of levodopa, carbidopa, and 3-OMD after administration of intra-jejunal administration of ABT-SLV187 (Day 21).
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: PK sample: participants who completed PK assessments in both the oral L/C and ABT-SLV187 Treatment Periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12/Dose0-12: Levodopa | 0.036 µg*h/mL/mg | Standard Deviation 0.008 |
| Oral Levodopa/Carbidopa Tablet | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12/Dose0-12: Carbidopa | 0.012 µg*h/mL/mg | Standard Deviation 0.003 |
| Oral Levodopa/Carbidopa Tablet | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12/Dose0-12: 3-OMD | 0.112 µg*h/mL/mg | Standard Deviation 0.029 |
| Oral Levodopa/Carbidopa Tablet | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16/Dose0-16: Levodopa | NA µg*h/mL/mg | — |
| Oral Levodopa/Carbidopa Tablet | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16/Dose0-16: Carbidopa | NA µg*h/mL/mg | — |
| Oral Levodopa/Carbidopa Tablet | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16/Dose0-16: 3-OMD | NA µg*h/mL/mg | — |
| Levodopa-carbidopa Intestinal Gel | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16/Dose0-16: Carbidopa | 0.008 µg*h/mL/mg | Standard Deviation 0.001 |
| Levodopa-carbidopa Intestinal Gel | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12/Dose0-12: Levodopa | 0.032 µg*h/mL/mg | Standard Deviation 0.006 |
| Levodopa-carbidopa Intestinal Gel | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16/Dose0-16: Levodopa | 0.035 µg*h/mL/mg | Standard Deviation 0.007 |
| Levodopa-carbidopa Intestinal Gel | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12/Dose0-12: Carbidopa | 0.008 µg*h/mL/mg | Standard Deviation 0.001 |
| Levodopa-carbidopa Intestinal Gel | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16/Dose0-16: 3-OMD | 0.125 µg*h/mL/mg | Standard Deviation 0.025 |
| Levodopa-carbidopa Intestinal Gel | AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12/Dose0-12: 3-OMD | 0.113 µg*h/mL/mg | Standard Deviation 0.022 |
Secondary
Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia
Participants were video recorded a total of 10 times for 1 to 2 minutes every 60 minutes while performing a standardized sequence of motor tasks. Based on these video recordings, a Video Evaluation Committee consisting of 3 neurologists individually evaluated the video under blinded conditions using the following assessments: Tremor at Rest (UPDRS item #20), Finger Taps (UPDRS #23), Rapid Alternating Movement of Hands (UPDRS #25), Arising from Chair (UPDRS #27), Gait (UPDRS #29), Postural Stability (UPDRS #30), Body Bradykinesia and Hypokinesia (UPDRS #31), and Dyskinesia (evaluated with the Goetz Dyskinesia Rating Scale). The UPDRS score is the sum of the answers to individual questions, each of which are measured on a 5-point scale (0-4), with higher scores associated with more disability. The Goetz Dyskinesia Rating Scale is a 5-point scale of the severity of dyskinesias, from 0 (absent) to 4 (violent dyskinesias).
Time frame: Baseline (Day -1), Endpoint (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Tremor at rest, Baseline | 0.00 units on a scale | Standard Deviation 0 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Tremor at rest, Endpoint | 0.00 units on a scale | Standard Deviation 0 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Finger taps, Baseline | 0.40 units on a scale | Standard Deviation 0.55 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Finger taps, Endpoint | 0.40 units on a scale | Standard Deviation 0.55 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Rapid alternating movement of hands, Baseline | 1.00 units on a scale | Standard Deviation 0 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Rapid alternating movement of hands, Endpoint | 0.60 units on a scale | Standard Deviation 0.55 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Arising from chair, Baseline | 0.10 units on a scale | Standard Deviation 0.22 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Arising from chair, Endpoint | 0.00 units on a scale | Standard Deviation 0 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Gait, Baseline | 0.60 units on a scale | Standard Deviation 0.55 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Gait, Endpoint | 0.60 units on a scale | Standard Deviation 0.55 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Postural stability, Baseline | 1.60 units on a scale | Standard Deviation 0.55 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Postural stability, Endpoint | 1.10 units on a scale | Standard Deviation 0.89 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Body bradykinesia and hypokinesia, Baseline | 1.00 units on a scale | Standard Deviation 0 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Body bradykinesia and hypokinesia, Endpoint | 0.80 units on a scale | Standard Deviation 0.27 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Dyskinesia, Baseline | 0.40 units on a scale | Standard Deviation 0.55 |
| Oral Levodopa/Carbidopa Tablet | Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia | Dyskinesia, Baseline | 0.90 units on a scale | Standard Deviation 0.55 |
Comparison: Rapid alternating movement of handsp-value: 0.5Wilcoxon one-sample test
Comparison: Arising from chairp-value: 1Wilcoxon one-sample test
Comparison: Postural stabilityp-value: 0.25Wilcoxon one-sample test
Comparison: Body bradykinesia and hypokinesiap-value: 0.5Wilcoxon one-sample test
Comparison: Dyskinesiap-value: 0.25Wilcoxon one-sample test
Secondary
Change From Baseline to the End of Treatment in Parkinson's Disease Diary Assessment
For each half hour period during 3 consecutive days prior to each assessment of the diary, participants (and/or their caregivers) entered into a diary whether they were asleep, in the ON motor state or in the OFF motor state in the following 5 grades: asleep, OFF, ON (no dyskinesia \[D\]), ON with non-troublesome dyskinesia (NTD), ON with troublesome dyskinesia (TD). ON time is when PD symptoms are well controlled by the drug. OFF time is when PD symptoms are not adequately controlled by the drug. Dyskinetic time is time with involuntary muscle movement. The ON or OFF times were calculated as the average of 3 daily times from the diaries. w/o = without, w/ = with
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in Parkinson's Disease Diary Assessment | Daily ON time w/o D + time w/ NTD + time w/ TD | 1.02 hours | Standard Deviation 3.73 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in Parkinson's Disease Diary Assessment | Daily OFF time | -1.02 hours | Standard Deviation 3.73 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in Parkinson's Disease Diary Assessment | Daily ON time w/o D + time w/ NTD | 0.76 hours | Standard Deviation 3.61 |
p-value: 0.574Paired t-test
Comparison: ON time w/o D + time with NTDp-value: 0.661Paired t-test
Comparison: ON time w/o D + time with NTD + time w/ TDp-value: 0.574Paired t-test
Secondary
Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients, including Mobility, Activities of Daily Living, Emotional Well-being, Stigma, Social Support, Cognition, Communication, and Bodily Discomfort, as well as a Summary Index Total Score. Scores for each are on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Total score | 1.26 units on a scale | Standard Deviation 5.48 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Mobility | 10.00 units on a scale | Standard Deviation 20.16 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Activities of daily living | -0.83 units on a scale | Standard Deviation 14.25 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Emotional well-being | -8.33 units on a scale | Standard Deviation 12.84 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Stigma | 1.25 units on a scale | Standard Deviation 10.27 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Social support | -5.00 units on a scale | Standard Deviation 6.85 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Cognition | -5.00 units on a scale | Standard Deviation 13.55 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Communication | 1.67 units on a scale | Standard Deviation 20.75 |
| Oral Levodopa/Carbidopa Tablet | Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores | Domain: Bodily discomfort | 8.33 units on a scale | Standard Deviation 30.62 |
Comparison: Total scorep-value: 0.636Paired t-test
Comparison: Domain: Mobilityp-value: 0.329Paired t-test
Comparison: Domain: Activities of daily livingp-value: 0.902Paired t-test
Comparison: Domain: Emotional well-beingp-value: 0.22Paired t-test
Comparison: Domain: Stigmap-value: 0.799Paired t-test
Comparison: Domain: Social supportp-value: 0.178Paired t-test
Comparison: Domain: Cognitionp-value: 0.456Paired t-test
Comparison: Domain: Communicationp-value: 0.866Paired t-test
Comparison: Domain: Bodily discomfortp-value: 0.576Paired t-test
Secondary
Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment
The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Baseline: Normal | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Baseline: Borderline ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Baseline: Mildly ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Baseline: Moderately ill | 2 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Baseline: Markedly ill | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Baseline: Severely ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Baseline: Among the most extremely ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Endpoint: Normal | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Endpoint: Borderline ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Endpoint: Mildly ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Endpoint: Moderately ill | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Endpoint: Markedly ill | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Endpoint: Severely ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-S, Endpoint: Among the most extremely ill | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-I: Very much improved | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-I: Much improved | 3 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-I: Minimally improved | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-I: No change | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-I: Minimally worse | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-I: Much worse | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment | CGI-I: Very much worse | 0 participants |
Secondary
Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187
Degree of Fluctuation (calculated as \[Cmax - Cmin\] / Cavg)) of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21).
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: PK sample: participants who completed PK assessments in both the oral L/C and ABT-SLV187 Treatment Periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Levodopa | 2.1 ratio | Standard Deviation 0.59 |
| Oral Levodopa/Carbidopa Tablet | Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Carbidopa | 0.97 ratio | Standard Deviation 0.2 |
| Oral Levodopa/Carbidopa Tablet | Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | 3-OMD | 0.48 ratio | Standard Deviation 0.1 |
| Levodopa-carbidopa Intestinal Gel | Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Levodopa | 0.38 ratio | Standard Deviation 0.16 |
| Levodopa-carbidopa Intestinal Gel | Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Carbidopa | 0.78 ratio | Standard Deviation 0.25 |
| Levodopa-carbidopa Intestinal Gel | Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | 3-OMD | 0.35 ratio | Standard Deviation 0.07 |
Secondary
Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the OFF and Dyskinesia States on the TRS I and the Normal, OFF, and Dyskinesia States on the TRS II
Participants were video recorded a total of 10 times for 1 to 2 minutes every 60 minutes while performing a standardized sequence of motor tasks: rest, finger taps, rapid alternating movement of hands, arising from chair and gait, including confirmation of postural stability. Based on these video recordings, a Video Evaluation Committee consisting of 3 neurologists individually evaluated the following Video Assessment and TRS under blinded conditions: Finger Taps, Rapid Alternating Movement of Hands, Arising from Chair, Gait, Body Bradykinesia and Hypokinesia, Dyskinesia for TRS I, with the addition of Tremor at Rest and Postural Stability for TRS II. The average of the 3 neurologists' evaluations was calculated as a percentage of ratings in the Normal state (ie, mild OFF to ON with mild dyskinesia), the Off state (moderate OFF to severe OFF), and the Dyskinesia state (ON with moderate dyskinesia to ON with severe dyskinesia) on the TRS I or II.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the OFF and Dyskinesia States on the TRS I and the Normal, OFF, and Dyskinesia States on the TRS II | TRS I OFF state | -15.33 percentage of ratings | Standard Deviation 13.04 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the OFF and Dyskinesia States on the TRS I and the Normal, OFF, and Dyskinesia States on the TRS II | TRS I Dyskinesia state | 0.00 percentage of ratings | Standard Deviation 4.71 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the OFF and Dyskinesia States on the TRS I and the Normal, OFF, and Dyskinesia States on the TRS II | TRS II Normal state | 14.67 percentage of ratings | Standard Deviation 18.65 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the OFF and Dyskinesia States on the TRS I and the Normal, OFF, and Dyskinesia States on the TRS II | TRS II OFF state | -15.33 percentage of ratings | Standard Deviation 18.65 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the OFF and Dyskinesia States on the TRS I and the Normal, OFF, and Dyskinesia States on the TRS II | TRS II Dyskinesia state | 0.67 percentage of ratings | Standard Deviation 1.49 |
Comparison: TRS I OFF statep-value: 0.058Paired t-test
Comparison: TRS I Dyskinesia statep-value: 1Paired t-test
Comparison: TRS II Normal statep-value: 0.153Paired t-test
Comparison: TRS II OFF statep-value: 0.14Paired t-test
Comparison: TRS II Dyskinesia statep-value: 0.374Paired t-test
Secondary
Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score ranges from 0-176, with 176 representing the worst (total) disability, and 0 no disability. The Part I Score is the sum of the answers to the 4 questions related to Mentation, Behavior and Mood, and ranges from 0-16. The Part II score is the sum of the answers to the 13 questions related to Activities of Daily Living, and ranges from 0-52. The Part III score is the sum of the 27 answers related to Motor Examination, and ranges from 0-108. The Part IV Score is the sum of the answers to the 11 questions related to Complications of Therapy, and ranges from 0-23. The Part IV dyskinesia subscore ranges from 0-12. For each part of the UPDRS, higher scores are associated with more disability.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores | Total score | -0.60 units on a scale | Standard Deviation 7.7 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores | Part I | 0.20 units on a scale | Standard Deviation 0.45 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores | Part II | 0.60 units on a scale | Standard Deviation 4.93 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores | Part II (Off-time) | -2.20 units on a scale | Standard Deviation 6.54 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores | Part III | -1.40 units on a scale | Standard Deviation 4.56 |
| Oral Levodopa/Carbidopa Tablet | Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores | Part IV subscore of dyskinesia | 2.20 units on a scale | Standard Deviation 2.39 |
Comparison: Total scorep-value: 0.87Paired t-test
Comparison: Part Ip-value: 0.374Paired t-test
Comparison: Part IIp-value: 0.799Paired t-test
Comparison: Part II (Off-time)p-value: 0.493Paired t-test
Comparison: Part IIIp-value: 0.53Paired t-test
Comparison: Part IV sub-score of dyskinesiap-value: 0.108Paired t-test
Secondary
Modified Hoehn and Yahr Staging at Baseline and End of Treatment
Participant's ON and OFF states staged according to the Modified Hoehn and Yahr criteria, an 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. ON time is when PD symptoms are well controlled by the drug. OFF time is when PD symptoms are not adequately controlled by the drug.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Modified Hoehn and Yahr Staging at Baseline and End of Treatment | ON state staging, Baseline | 2.5 units on a scale |
| Oral Levodopa/Carbidopa Tablet | Modified Hoehn and Yahr Staging at Baseline and End of Treatment | ON state staging, Endpoint | 3.0 units on a scale |
| Oral Levodopa/Carbidopa Tablet | Modified Hoehn and Yahr Staging at Baseline and End of Treatment | OFF state staging, Baseline | 4.0 units on a scale |
| Oral Levodopa/Carbidopa Tablet | Modified Hoehn and Yahr Staging at Baseline and End of Treatment | OFF state staging, Endpoint | 4.0 units on a scale |
Comparison: On state stagingp-value: 1Wilcoxon one-sample test
Comparison: Off state stagingp-value: 1Wilcoxon one-sample test
Secondary
Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: ABT-SLV187 safety sample: participants who had at least one dose of the ABT-SLV187 study medication after the baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any PQC | 2 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any PQC related to an AE | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any serious PQC | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any PQC leading to discontinuation of study drug | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any PQC by pump | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any PQC by NJ-tube insertion | 2 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any PQC by adapter | 0 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Any PQC by cassettes | 1 participants |
| Oral Levodopa/Carbidopa Tablet | Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period | Without any PQCs | 4 participants |
Secondary
Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187
Cmax, Cavg, Cmin, and Cmin (2-12 hours) of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21). Cmin values for levodopa and carbidopa during the 16 hours of infusion were observed either at time 0 or 15 min after start of the infusion and were a result of drug washout prior to establishment of infusion.
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: PK sample: participants who completed PK assessments in both the oral L/C and ABT-SLV187 Treatment Periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmax: Levodopa | 5.96 µg/mL | Standard Deviation 0.77 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmax: Carbidopa | 0.128 µg/mL | Standard Deviation 0.03 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmax: 3-OMD | 9.27 µg/mL | Standard Deviation 2.17 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cavg: Levodopa | 2.37 µg/mL | Standard Deviation 0.26 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cavg: Carbidopa | 0.079 µg/mL | Standard Deviation 0.02 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cavg: 3-OMD | 7.36 µg/mL | Standard Deviation 1.93 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin: Levodopa | 0.268 µg/mL | Standard Deviation 0.43 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin: Carbidopa | 0.014 µg/mL | Standard Deviation 0.02 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin: 3-OMD | 5.67 µg/mL | Standard Deviation 1.6 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin (2-12 hours): Levodopa | 0.734 µg/mL | Standard Deviation 0.43 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin (2-12 hours):Carbidopa | 0.050 µg/mL | Standard Deviation 0.02 |
| Oral Levodopa/Carbidopa Tablet | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin (2-12 hours): 3-OMD | 5.72 µg/mL | Standard Deviation 1.53 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin (2-12 hours):Carbidopa | 0.130 µg/mL | Standard Deviation 0.04 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmax: Levodopa | 4.38 µg/mL | Standard Deviation 1.15 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin: Levodopa | 0.061 µg/mL | Standard Deviation 0.03 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmax: Carbidopa | 0.273 µg/mL | Standard Deviation 0.07 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin (2-12 hours): Levodopa | 2.38 µg/mL | Standard Deviation 0.77 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmax: 3-OMD | 11.7 µg/mL | Standard Deviation 1.25 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin: Carbidopa | 0.016 µg/mL | Standard Deviation 0.01 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cavg: Levodopa | 2.87 µg/mL | Standard Deviation 0.66 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin (2-12 hours): 3-OMD | 8.14 µg/mL | Standard Deviation 0.94 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cavg: Carbidopa | 0.172 µg/mL | Standard Deviation 0.04 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cmin: 3-OMD | 7.78 µg/mL | Standard Deviation 0.63 |
| Levodopa-carbidopa Intestinal Gel | Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | Cavg: 3-OMD | 9.80 µg/mL | Standard Deviation 1.23 |
Secondary
Ratio of Metabolite 3-OMD to Levodopa (M/P [AUC0-12]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187
M/P (AUC0-12) after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21).
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: PK sample: participants who completed PK assessments in both the oral L/C and ABT-SLV187 Treatment Periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Ratio of Metabolite 3-OMD to Levodopa (M/P [AUC0-12]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | 3.11 ratio | Standard Deviation 0.71 |
| Levodopa-carbidopa Intestinal Gel | Ratio of Metabolite 3-OMD to Levodopa (M/P [AUC0-12]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | 3.53 ratio | Standard Deviation 0.7 |
Secondary
Schwab and England Activities of Daily Living Scale at Baseline and End of Treatment
The Schwab and England scale was used to rate the subject's activities of daily living by recording the percentage score, ranging between being completely independent (100%) and totally dependent (10%).
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: Full Analysis Set: participants who had data for baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Schwab and England Activities of Daily Living Scale at Baseline and End of Treatment | Baseline | 80.0 units on a scale |
| Oral Levodopa/Carbidopa Tablet | Schwab and England Activities of Daily Living Scale at Baseline and End of Treatment | Endpoint | 80.0 units on a scale |
p-value: 0.125Wilcoxon one-sample test
Secondary
The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187
AUC0-12 and AUC0-16 of levodopa, carbidopa, and 3-OMD after administration of the oral L/C tablets (Day -1) and intra-jejunal administration of ABT-SLV187 (Day 21).
Time frame: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Population: PK sample: participants who completed PK assessments in both the oral L/C and ABT-SLV187 Treatment Periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12: Levodopa | 28.4 µg*h/mL | Standard Deviation 3.08 |
| Oral Levodopa/Carbidopa Tablet | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12: Carbidopa | 0.94 µg*h/mL | Standard Deviation 0.18 |
| Oral Levodopa/Carbidopa Tablet | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12: 3-OMD | 88.3 µg*h/mL | Standard Deviation 23.1 |
| Oral Levodopa/Carbidopa Tablet | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16: Levodopa | NA µg*h/mL | — |
| Oral Levodopa/Carbidopa Tablet | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16: Carbidopa | NA µg*h/mL | — |
| Oral Levodopa/Carbidopa Tablet | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16: 3-OMD | NA µg*h/mL | — |
| Levodopa-carbidopa Intestinal Gel | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16: Carbidopa | 2.80 µg*h/mL | Standard Deviation 0.666 |
| Levodopa-carbidopa Intestinal Gel | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12: Levodopa | 34.4 µg*h/mL | Standard Deviation 7.95 |
| Levodopa-carbidopa Intestinal Gel | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16: Levodopa | 46.7 µg*h/mL | Standard Deviation 10.7 |
| Levodopa-carbidopa Intestinal Gel | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12: Carbidopa | 2.07 µg*h/mL | Standard Deviation 0.52 |
| Levodopa-carbidopa Intestinal Gel | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-16: 3-OMD | 165 µg*h/mL | Standard Deviation 21.2 |
| Levodopa-carbidopa Intestinal Gel | The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187 | AUC0-12: 3-OMD | 118 µg*h/mL | Standard Deviation 14.7 |
Secondary
Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187
Tmax of levodopa, carbidopa, and its metabolite 3-O-methyldopa (3-OMD) after administration of oral L/C tablets and intra-jejunal administration of ABT-SLV187.
Time frame: Baseline (Day -1): pre-dose; 15, 30, 45, 60 mins post-morning dose; every 30 mins thereafter for 12 hrs. Day 21: pre-dose; 15, 30, 45, 60 mins post-infusion; every 30 mins from hrs 1 to 12 post-infusion; every 2 hrs from 12 to 16 hrs post-infusion.
Population: Pharmacokinetic (PK) sample: participants who completed PK assessments in both the oral L/C and ABT-SLV187 Treatment Periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Levodopa/Carbidopa Tablet | Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187 | Levodopa | 3.0 hours | Standard Deviation 3.5 |
| Oral Levodopa/Carbidopa Tablet | Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187 | Carbidopa | 7.8 hours | Standard Deviation 2.8 |
| Oral Levodopa/Carbidopa Tablet | Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187 | 3-OMD | 11 hours | Standard Deviation 0.76 |
| Levodopa-carbidopa Intestinal Gel | Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187 | 3-OMD | 11 hours | Standard Deviation 0.79 |
| Levodopa-carbidopa Intestinal Gel | Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187 | Levodopa | 1.0 hours | Standard Deviation 0.5 |
| Levodopa-carbidopa Intestinal Gel | Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187 | Carbidopa | 4.5 hours | Standard Deviation 4.2 |