1) To Identify the Concentration of CD That Provides Optimal Bioavailability of a Concomitant Fixed Concentration of LD Infused SC Continuously; 2) To Compare the Bioavailability of the Optimal LD/CD Solution to That of LD/CD Intestinal Gel

ND0612-005

An Open-Label Study in Healthy Male and Female Subjects to Identify the Concentration that Provides Optimal Bioavailability of Levodopa Infused Subcutaneously via a Pump System; and to Compare the Bioavailability of Levodopa/Carbidopa Solution to that of Levodopa/Carbidopa Intestinal Gel (LCIG), Infused via a Naso-Jejunal Tube

2015-05-29

2016-06-30

2016-06-30

Completed

Early phase I

36

Inclusion Criteria: Inclusion Criteria: Part 1 ND0612-005a: 1. Healthy males or non-pregnant, non-lactating healthy females 2. Age 40 to 65 years of age 3. Body mass index of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator 4. Must be willing and able to communicate and participate in the whole study (Part 1 only for subjects assigned to ND0612L and Part 1 and Part 2 for subjects assigned to ND0612H) 5. Must provide written informed consent 6. Area of administration to be evaluable for local skin reaction (normal skin without skin burns, scars or large tattoos in the area of administration) 7. Must agree to use an adequate method of contraception Inclusion Criteria: Part 2 ND0612-005b: 1. Subjects who were dosed with ND0612H (any replacements subjects enrolled in Part 2 will be dosed with the optimal LD/CD concentration of ND0612H after completion of Part 2). Exclusion Criteria: 1. Participation in a clinical research study within the previous 3 months 2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee 3. Subjects who have previously been enrolled in this study 4. History of any drug or alcohol abuse in the past 2 years 5. Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) 6. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening 7. Females of childbearing potential who are pregnant or lactating (female subjects must have a negative urine pregnancy test at admission) 8. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1) 9. Positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1) 10. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results 11. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening 12. History of cardiovascular, renal, hepatic, chronic respiratory or GI disease as judged by the investigator 13. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 14. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active 15. Donation or loss of greater than 400 mL of blood within the previous 3 months 16. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol, hormone replacement therapy and hormonal contraception) or herbal remedies in the 14 days before IMP administration (See Section 11.4). Exceptions may apply on a case by case basis if considered not to interfere with the objectives of the study as agreed by the PI and sponsor's medical monitor 17. Use of any non-selective monoamine oxidase (MAO) inhibitors within 2 weeks of screening 18. History or presence of glaucoma 19. History or presence of suspicious undiagnosed skin lesions or a history of melanoma 20. Any history of psychoses or seizure 21. Known hypersensitivity to Sinemet® or domperidone or any of the excipients 22. Any history or presence of Prolactin-releasing pituitary tumour (prolactinoma) 23. Any medical history of GI haemorrhage, mechanical obstruction or perforation 24. Any history of moderate or severe hepatic impairment 25. Subjects with clinically significant liver function tests 26. Subjects with QTc \>450 ms at screening 27. Subjects with significant electrolyte disturbances 28. Subjects with any underlying cardiac disease 29. Subjects who have received QT-prolonging drugs or potent cytochrome P450 (CYP) 3A4 inhibitors within 4 weeks of screening 30. ND0612H arm only: Subjects who have sinus problems 31. ND0612H arm only: Subjects who have regular heartburn and/or indigestion 32. ND0612H arm only: Subjects who have had abdominal (bowel) surgery 33. ND0612H arm only: Any clinically significant findings observed during naso-jejunal tube placement as determined by the endoscopist 34. Failure to satisfy the investigator of fitness to participate for any other reason

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 36, 'type': 'ACTUAL'}}

2024-01-18