Effectiveness and Pharmacokinetics Parameters of WD- 1905 Tablets with SINEMET® (carbidopa and levodopa) Tablets in Parkinsons Disease (PD) Subjects with Morning Akinesia.
- Conditions
- Health Condition 1: G20- Parkinsons disease
- Registration Number
- CTRI/2023/12/060430
- Lead Sponsor
- Shanghai WD Pharmaceutical Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Male or non-pregnant, non-lactating female between = 30 and = 75 years of age.
2. Clinical diagnosis of idiopathic PD consistent with the UK PD Brain Bank Society.
3. Clinically meaningful response to levodopa.
4. Receiving stable daily doses of levodopa =450 mg and =1500 mg divided to at least three times a day during daytime at least 4 weeks before study participation.
5. May be receiving other concomitant anti-PD medications except for non-selective Mono Amino Oxidase (MAO) inhibitors (must be discontinued for at least 30 days prior to screening).
6. Well-defined early morning OFF ? (morning akinesia) persists at least 3 weeks as recorded by subject’s diary and determined by the Investigator before study drug administration.
7. Experience predictable OFF episodes in early morning on awakening prior to receiving morning dose of levodopa.
8. Total duration of = 3 hours’ OFF-time each day, based on the OFF-time diary (Hauser Diary/patient motor diary) collected over 3 consecutive days (Day-3 to Day -1) during the screening period.
9. Stage 4 or less on the Hoehn and Yahr scale in the ON state.
10. Mini Mental State Examination (MMSE) = 25 as assessed by Investigator during screening.
11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study related procedures to complete the study.
12. Male or female of childbearing potential willing to use adequate methods of contraception throughout the study
13. Subject/LAR able to understand the consent form, and to provide written informed consent.
Exclusion Criteria:
1. Known hypersensitivity to levodopa or carbidopa.
2. Atypical or secondary Parkinsonism.
3. History of intracranial surgical intervention for PD or other indications (pallidotomy, thalamotomy, deep brain stimulation, etc).
4. Changes in levodopa or other PD drug dosing regimens 4 weeks before the screening visit.
5. Any history of sleep attacks, impulse control issues, or hypersexuality.
6. Subject has undergone neurosurgery for the treatment of PD.
7. Subject has any neurological deficit that might interfere with the study assessments (e.g., hemiparesis).
8. Subject has contraindications to levodopa, (e.g., narrow angle glaucoma, malignant melanoma).
9. Participation in any other clinical trial within 30 days of the screening visit or administration of an investigational product in another trial within 30 days or 5 half-lives (whichever is longer) prior to the screening visit.
10. Drug or alcohol dependency in the past 6 months.
11. Presence of significant orthostatic hypotension (i.e., decrease in systolic blood pressure =20 mmHg or diastolic BP of =10 mmHg when comparing standing to supine values within 3 minutes).
12. A history of gastric surgery, including bariatric surgery within the past year.
13. A positive screen for hepatitis (includes subtypes B & C) or HIV antibody.
14. Malignant melanoma or a history of previously treated malignant melanoma within 5 years.
15. Clinically significant medical, surgical or laboratory abnormality in the judgment of the Investigator.
16. History of suicidal ideation or attempted suicide within the previous 12 months.
17. Psychiatric disorder, including but not limited to dementia or any disorder that, in the opinion of the Investigator requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
18. Severe dyskinesia (defined as per MDS-UPDRS Part-III) that would significantly interfere with the subjects ability to perform study assessments.
19. Consumption of grapefruit, grapefruit-like or grapefruit containing products within 7 days prior to initial drug administration throughout the study duration.
20. Ingestion of any alcoholic, caffeine or xanthine containing food or beverage for at least 48 hours prior to the initial dose of study medication to throughout the study duration.
21. Use of any drugs affecting the Absorption, Distribution, Metabolism and Excretion (ADME) of levodopa and carbidopa within 30 days prior to receiving the first dose of study medication. They can be allowed depending on Principal Investigator’s discretion in consultation with medical monitor if they are kept constant in the last 30 days and are expected to remain constant during the study period.
22. Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 90 days prior to screening.
23. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
24. History of difficulty in swallowing of study medication, or any other gastrointestinal disease, which could affect drug absorption.
25. Laboratory test abnormalities at screening (Visit 1) deemed clinically significant judged by the Investigator.
26. Any other condition that, in the Investigator’s judgment, might increa
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method . The change in % OFF-time (6 AM to 9 AM) from baseline (the <br/ ><br>average of Day -3 to Day -1 data) to Day 7 and to Day 20, using <br/ ><br>the patient motor diary and Investigator Assessment of Subjects Motor State (IASMS) data will be analyzed using Analysis of covariance (ANCOVA) models using baseline values as covariate and treatment as fixed effect. <br/ ><br>Timepoint: 3 week
- Secondary Outcome Measures
Name Time Method 1. To compare Tmax, ss of WD-1905 tablets relative to that of SINEMET® (carbidopa and levodopa) Tablets on Day 5 and Day 18, after the oral administration before sleep. <br/ ><br>2. To compare relative bioavailability in Cmaxss and AUCtauss between Treatments (A vs. B) on Day 5 and Day 18, after the oral administration at bedtime before sleep. <br/ ><br>3. To compare other pharmacokinetic parameters between Treatments (A vs. B) on Day 5 and Day 18, after the oral administration at bedtime before sleep between Day 1 to Day 7 and from Day 14 to Day 20.7 <br/ ><br>Timepoint: Day 5 and Day 18, 13 blood samples (5 mL each) will be collected at the following time points: at pre-dose and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, and 12.0 hours post dose.