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This study will investigate the drug-drug interactions (DDIs) between rucaparib and oral rosuvastatin (Arm A), and between rucaparib and oral ethinylestradiol and levonorgestrel (Arm B), with rucaparib as a perpetrator.
This is a Phase 1, open-label, drug-drug-interaction (DDI) study in patients with advanced solid tumor. In Part I, the effects of rucaparib (600 mg twice daily [BID]) on the PK of oral rosuvastatin (Arm A) and the combined oral contraceptives (ethinylestradiol and levonorgestrel; Arm B) will be assessed.
Part I: patients will receive single oral doses of rosuvastatin or oral contraceptives (according to assigned arm) on Day 1 and Day 19. Continuous treatment with rucaparib at 600 mg BID will commence on Day 5 and continue until the end of Part I (Day 23).
Part II (optional): treatment with rucaparib in 28-day cycles may continue (at the discretion of the Investigator) until progression of disease, unacceptable toxicity, or other reason for discontinuation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A - rucaparib and oral rosuvastatin | Other |
| |
| Arm B - rucaparib and oral contraceptives | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rucaparib | Drug | Rucaparib 600 mg BID commencing on Day 5 until Day 23. |
|
| Measure | Description | Time Frame |
|---|---|---|
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | Maximum plasma concentration (Cmax) | Day 1 to Day 23 |
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | Area under the concentration-time curve (AUC) from time zero up to the last time point with a quantifiable concentration (AUC0-last) | Day 1 to Day 23 |
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | AUC up to time infinity, with extrapolation of the terminal phase (AUC0-inf) | Day 1 to Day 23 |
| Measure | Description | Time Frame |
|---|---|---|
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | Terminal half-life (t1/2) | Day 1 to Day 23 |
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. |
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Inclusion Criteria (All patients):
Inclusion Criteria (Arm A):
- Male or female patients ≥ 18 years of age
Inclusion Criteria (Arm B):
- Female patients ≥ 18 years of age
Exclusion Criteria (All patients):
Exclusion Criteria (Arm A):
Exclusion Criteria (Arm B):
Both male and female patients are eligible for Arm A. Female patients only are eligible for Arm B.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Magyarország Fázis I-es Klinikai Farmakológiai Vizsgálóhely FMC Dialízis Központ, II. em. | Budapest | 1076 | Hungary | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34370076 | Derived | Liao M, Jeziorski KG, Tomaszewska-Kiecana M, Lang I, Jasiowka M, Skarbova V, Centkowski P, Ramlau R, Gornas M, Lee J, Edwards S, Habeck J, Nash E, Grechko N, Xiao JJ. A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2021 Nov;88(5):887-897. doi: 10.1007/s00280-021-04338-7. Epub 2021 Aug 9. |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C531549 | rucaparib |
| D000068718 | Rosuvastatin Calcium |
| D003276 | Contraceptives, Oral |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
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|
| Rosuvastatin | Drug | Single dose of 20mg oral rosuvastatin on Day 1 and Day 19 only. |
|
|
| Oral Contraceptives | Drug | Single dose of combined oral contraceptive (30 μg ethinylestradiol and 150 μg levonorgestrel) on Day 1 and Day 19 only. |
|
Time to occurrence of Cmax (tmax) |
| Day 1 to Day 23 |
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | Apparent total clearance of drug after oral administration (CL/F) | Day 1 to Day 23 |
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | Apparent volume of distribution during terminal phase (Vz/F) | Day 1 to Day 23 |
| The following secondary PK parameter will be calculated for rucaparib. | Trough plasma concentration (Cmin) | Day 1 to Day 23 |
| Incidence of Adverse Events [Safety and Tolerability] | From Day 1 to last patient visit in Part II (approximately 2 years) |
| Incidence of clinical laboratory abnormalities [Safety and Tolerability] | From Day 1 to last patient visit in Part II (approximately 2 years) |
| Incidence of dose modifications [Safety and Tolerability] | From Day 1 to last patient visit in Part II (approximately 2 years) |
| Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej |
| Biała Podlaska |
| 21-500 |
| Poland |
| BioVirtus Centrum Medyczne | Józefów | 05-410 | Poland |
| Ujastek Sp. z o.o. Centrum medyczne | Krakow | 31-752 | Poland |
| Med Polonia Sp. z o.o. | Poznan | 60-693 | Poland |
| Zdrowie Kobiety Centrum Leczniczo-Rehabilitacyjne i Medycyny Pracy ATTIS Sp. z o.o., Zakład Onkologii Kobiecej | Warsaw | 01-401 | Poland |
| Summit Clinical Research s.r.o. | Bratislava | 831 01 | Slovakia |
| D006845 |
| Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003271 | Contraceptive Agents, Female |
| D003270 | Contraceptive Agents |
| D012102 | Reproductive Control Agents |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045506 | Therapeutic Uses |