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| Name | Class |
|---|---|
| Avance Clinical Pty Ltd. | INDUSTRY |
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This is a Phase 1, open-label, 3-period study to determine radiprodil's potential to act as a perpetrator of cytochrome P-450 (CYP) metabolic pathways and transporter pathways. The study will evaluate the pharmacokinetics (PK) and safety effects of co-administration of radiprodil with oral midazolam, rosuvastatin, warfarin, digoxin, and omeprazole in healthy adult subjects. The study will be conducted in 1 cohort of healthy adult participants only.
This is a Phase 1, open-label, 3-period study to evaluate the PK and safety effects of co-administration of radiprodil with oral midazolam, rosuvastatin, warfarin, digoxin, and omeprazole in healthy adult subjects. The study will be conducted at a single site.
The study will be conducted in 1 cohort of participantsUp to 18 male or female healthy adults are planned to be recruited in this study. Participants will be required to be in the study for up to 80 days, which includes a 27-day screening period, 24-day confinement period, and a follow-up phone call 30 days (± 2 days) after the last dose of study drug. Study drugs will be administered using a sequential cocktail approach consisting of substrates of multiple CYP enzymes or transporters.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Cohort | Experimental | Study Drug - Radiprodil will be administred using a sequential cocktail approach consisting of substrates of multipleCYP enzymes or transporters. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiprodil + co-administered drugs | Drug | Study drug radiprodil will be administered asbelow in a sequential manner. - Radiprodil 7.5 mg, 15 mg and 30 mg will be administered in a sequential manner. Co-administered drugs include: - Warfarin - 10 mg tablets, midazolam 1 mg, digoxin 0.25 mg, rosuvastatin 10 mg, omeprazole 20 mg, Vitamin K - 10 mg. |
| Measure | Description | Time Frame |
|---|---|---|
| To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of warfarin following repeated oral doses of radiprodil. | Blood samples will be assessed. | Day1 - Predose, 0.5 hour,1 hour, 1.5, 2, 3, 4, 8, 12 Day 15 - 24 hours post dose, 48 hour, 96, 120, 144 hours |
| To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of warfarin following repeated oral dosing of radiprodil. | Blood plasma samples will be assessed | Blood samples for plasma PK will be collected on the following days. - S-warfin - Day1 - Predose, 0.5 hour,1 hour, 1.5, 2, 3, 4, 8, 12 Day 15 - 24 hours post dose, 48 hour, 96, 120, 144 hours |
| To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of midazolam following repeated oral doses of radiprodil. | Blood plasma samples will be assessed | Day 1 - Pre-dose, 0.5, 1, 1.5, 2, 3, 4 , 8, 12, 24 hour day 15- 24 hour post dose - |
| To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of midazolam following repeated oral dosing of radiprodil | Blood plasma samples will be assessed | Day 1 - Pre-dose, 0.5, 1, 1.5, 2, 3, 4 , 8, 12, 24 hour day 15- 24 hour post dose -Digoxin- Day 3- predose, 0.5 hour, 1 , 1.5, 2,3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose. |
| To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of digoxin following repeated oral doses of radiprodil. | Blood plasma samples will be assessed | Day 3- predose, 0.5 hour, 1 , 1.5, 2,3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose |
| Measure | Description | Time Frame |
|---|---|---|
| To assess the safety of oral dosing of radiprodil co-administered with midazolam. | Safety will be evaluated by: Incidence, severity and relationship of AEs, serious adverse events (SAEs), AESI, and withdrawals due to AEs | Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose. |
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Inclusion Criteria: - Healthy male and female adults between 18 and 55 years of age, inclusive, at Screening.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nucleus Network Melbourne | Melbourne | Victoria | 3004 | Australia |
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Study drugs will be administered using a sequential cocktail approach consisting of substrates of multipleCYP enzymes or transporters.
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Open-label study
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|
| To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of digoxin following repeated oral dosing of radiprodil. |
Blood plasma samples will be assessed |
| Day 3- predose, 0.5 hour, 1 , 1.5, 2,3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose |
| To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of rosuvastatin following repeated oral doses of radiprodil. | Blood plasma samples will be assessed | Day 3 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose |
| To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of rosuvastatin following repeated oral dosing of radiprodil | Blood plasma samples will be assessed | Day 3 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose |
| To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of omeprazole following repeated oral doses of radiprodil. | Blood plasma samples will be assessed | Day 5 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 19 - 24 hourpost dose |
| To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of omeprazole following repeated oral dosing of radiprodil. | Blood plasma samples will be assessed | Day 5 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 19 - 24 hourpost dose |
| To assess the safety of oral dosing of radiprodil co-administered with digoxin | Safety will be evaluated by: • Incidence, severity and relationship of AEs, serious adverse events (SAEs), AESI, and withdrawals due to AEs | Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose |
| To assess the safety of oral dosing of radiprodil co-administered with rosuvastatin. | Safety will be evaluated by Incidence, severity and relationship of AEs, serious adverse events (SAEs), AESI, and withdrawals due to AEs | Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose |
| To assess the safety of oral dosing of radiprodil co-administered with omeprazole | Safety will be evaluated by Incidence, severity and relationship of AEs, serious adverse events (SAEs), AESI, and withdrawals due to AEs. | Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose. |
| To assess the safety of oral dosing of radiprodil co-administered with oral warfarin. | Safety will be evaluated by Incidence, severity and relationship of AEs, serious adverse events (SAEs), AESI, and withdrawals due to AEs. | Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose. |
| 12-lead ECG - Mean change in QT interval from baseline to end of treatment (oral dosing of radiprodil co-administered with midazolam) | 12 lead ECG- Screening, Day -1, Day 1, Day 3, Day 5, Day 7-8, 9-10, 11-14, 15, 17, 19 and Day 24 (End of Study Visit/Early Termination Visit) |
| 12-lead ECG - Mean change in QT interval from baseline to end of treatment (oral radiprodil co-administered with digoxin) | 12 lead ECG- Screening, Day -1, Day 1, Day 3, Day 5, Day 7-8, 9-10, 11-14, 15, 17, 19 and Day 24 (End of Study Visit/Early Termination Visit) |
| 12-lead ECG- Mean change from Baseline to End-of-Treatment in QT interval(oral dosing of radiprodil co-administered with rosuvastatin) | 12 lead ECG- Screening, Day -1, Day 1, Day 3, Day 5, Day 7-8, 9-10, 11-14, 15, 17, 19 and Day 24 (End of Study Visit/Early Termination Visit) |
| 12-lead ECG- Mean change from Baseline to End-of-Treatment in QT interval (oral dosing of radiprodil co-administered with omeprazole) | 12 lead ECG- Screening, Day -1, Day 1, Day 3, Day 5, Day 7-8, 9-10, 11-14, 15, 17, 19 and Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with oral warfarin | Change from baseline in clinical laboratory parameters(hematology, coagulation, clinical chemistry, and urinalysis). Clinical laboratory results assessed using blood and urine samples and will be classified as normal, abnormal not clinically significant (NCS), or abnormal CS. | Clinical lab parameters- Screening, Day -1, Days 2-4, Days 6-14,Days 16-18, Days 20-21 and Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with midazolam | Change from baseline in clinical laboratory parameters(hematology, coagulation, clinical chemistry, and urinalysis). Clinical laboratory results assessed using blood and urine samples and will be classified as normal, abnormal not clinically significant (NCS), or abnormal CS. | Clinical lab parameters- Screening, Day -1, Days 2-4, Days 6-14,Days 16-18, Days 20-21 and Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with digoxin | Change from baseline in clinical laboratory parameters(hematology, coagulation, clinical chemistry, and urinalysis). Clinical laboratory results assessed using blood and urine samples and will be classified as normal, abnormal not clinically significant (NCS), or abnormal CS. | Clinical lab parameters- Screening, Day -1, Days 2-4, Days 6-14,Days 16-18, Days 20-21 and Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with rosuvastatin | Change from baseline in clinical laboratory parameters(hematology, coagulation, clinical chemistry, and urinalysis). Clinical laboratory results assessed using blood and urine samples and will be classified as normal, abnormal not clinically significant (NCS), or abnormal CS. | Clinical lab parameters- Screening, Day -1, Days 2-4, Days 6-14,Days 16-18, Days 20-21 and Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with omeprazole | Clinical laboratory results assessed using blood and urine samples and will be classified as normal, abnormal not clinically significant (NCS), or abnormal CS. | Clinical lab parameters- Screening, Day -1, Days 2-4, Days 6-14,Days 16-18, Days 20-21 and Day 24 (End of Study Visit/EarlyTermination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with oral warfarin. | C-SSRS scores are assessed using the 'baseline-screening' version and the 'since last visit' version at each scheduled time point. | Day -1,Day 15, Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with midazolam | C-SSRS scores are assessed using the 'baseline-screening' version and the 'since last visit' version at each scheduled time point. | Day -1,Day 15, Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with digoxin. | C-SSRS scores are assessed using the 'baseline-screening' version and the 'since last visit' version at each scheduled time point. | Day -1,Day 15, Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with rosuvastatin | C-SSRS scores are assessed using the 'baseline-screening' version and the 'since last visit' version at each scheduled time point. | Day -1,Day 15, Day 24 (End of Study Visit/Early Termination Visit) |
| To assess the safety of oral dosing of radiprodil co-administered with omeprazole | C-SSRS scores are assessed using the 'baseline-screening' version and the 'since last visit' version at each scheduled time point. | Day -1,Day 15, Day 24 (End of Study Visit/Early Termination Visit) |
| ID | Term |
|---|---|
| D014402 | Tuberous Sclerosis |
| D000092222 | Focal Cortical Dysplasia |
| ID | Term |
|---|---|
| D006222 | Hamartoma |
| D009369 | Neoplasms |
| D009378 | Neoplasms, Multiple Primary |
| D009386 | Neoplastic Syndromes, Hereditary |
| D065703 | Malformations of Cortical Development, Group I |
| D054220 | Malformations of Cortical Development |
| D009421 | Nervous System Malformations |
| D009422 | Nervous System Diseases |
| D020752 | Neurocutaneous Syndromes |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
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| ID | Term |
|---|---|
| C000626801 | radiprodil |
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