Mass Balance, Pharmacokinetics, Biotransformation and Bioavailability Study of ODM-201 in Healthy Male Subjects

Keywords

• volunteers

Lead sponsor

Orion Corporation, Orion Pharma is the lead sponsor of 100 studies on the registry; 3 are open to participants now.

Eligibility criteria

Study arms

• Experimental
  Part 1

  A single oral 300 mg tablet of ODM-201 followed by single intravenous 100 microg of 14C-ODM-201 containing not more than 37 kBq (1000 nCi)14C

  Drug: ODM-201 300 mg tablet · Drug: intravenous14C-ODM-201

• Experimental
  Part 2

  A single oral solution of 300 mg 14C-ODM-201 containing no more than 6.3 MBq (171 microCi) 14C

  Drug: 300 mg 14C-ODM-201 oral solution

Interventions

• DrugODM-201 300 mg tablet
• Drugintravenous14C-ODM-201
• Drug300 mg 14C-ODM-201 oral solution

Primary outcomes

1. Amount of 14C-ODM-201 dose excreted and cumulative amount excreted in urine and faeces and total. Amount excreted and cumulative amount excreted in urine, faeces and total expressed as a percentage of the administered dose.

   Time frame: Urine and faecal samples are collected baseline (Day-1) 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing

Other outcomes

1. Metabolite profile of 14C-ODM-201 in plasma, urine and faeces

   Time frame: up to 14 days post-dose after oral solution dosing

2. Maximum concentration (Cmax) of 14C-radioactivity in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing

3. Time to maximum concentration (tmax) of 14C-radioactivity in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing

4. Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing

5. Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-radioactivity in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing

6. Half life (t1/2) of 14C-radioactivity in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing

7. Maximum concentration (Cmax) of ODM-201 in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

8. Time to maximum concentration (tmax) of ODM-201 in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

9. Area under the plasma concentration-time curve (AUC(0-t)) of ODM-201 in plasma

   Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

10. Area under the plasma concentration-time curve (AUC(0-infinity)) of ODM-201 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

11. Half life (t1/2) of ODM-201 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

12. Maximum concentration (Cmax) of metabolite ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

13. Time to maximum concentration (tmax) of metabolite ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

14. Area under the plasma concentration-time curve (AUC(0-t)) of metabolite ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

15. Area under the plasma concentration-time curve (AUC(0-infinity)) of metabolite ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

16. Half life (t1/2) of metabolite ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing

17. Maximum concentration (Cmax) of metabolite 14C-ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

18. Time to maximum concentration (tmax) of metabolite 14C-ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

19. Area under the plasma concentration-time curve (AUC(0-t)) of metabolite 14C-ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

20. Area under the plasma concentration-time curve (AUC(0-infinity)) of metabolite 14C-ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

21. Half life (t1/2) of metabolite 14C-ORM 15341 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

22. Maximum concentration (Cmax) of 14C-ODM-201 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

23. Time to maximum concentration (tmax) of 14C-ODM-201 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

24. Area under the plasma concentration-time curve (AUC(0-t)) of 14C-ODM-201 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

25. Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-ODM-201 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

26. Half life (t1/2) of 14C-ODM-201 in plasma

    Time frame: The samples were taken 72 h post-dose after IV dosing

27. Maximum concentration (Cmax) of 14C-radioactivity in whole blood

    Time frame: The samples were taken 24 h post-dose after oral solution dosing

28. Time to maximum concentration (tmax) of 14C-radioactivity in whole blood

    Time frame: The samples were taken 24 h post-dose after oral solution dosing

29. Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in whole blood

    Time frame: The samples were taken 24 h post-dose after oral solution dosing

30. Renal elimination for ODM-201 in urine

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 14 d post-dose after oral solution dosing

31. Renal elimination for 14C-ODM-201 in urine

    Time frame: The samples were taken up-to 14 d post-dose after oral solution dosing

32. Fraction absorbed (FA) of total radioactivity based on urinary recovery of total radioactivity for both IV and oral dosing

    Time frame: The samples were taken 72 h post-dose after IV dosing and up-to 14 d post-dose after oral solution dosing

33. Adverse events

    Time frame: Collected 7 days post-dose in part 1 and up to 14 days post-dose in part 2

34. Physical examination

    Full physical examination

    Time frame: Assessed at screening, pre-dose, at discharge from the study centre (72 h and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2)

35. Blood pressure

    Time frame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose

36. Heart rate

    Time frame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose

37. Oral temperature

    Time frame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose

38. 12-lead ECG

    Time frame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose

39. Clinical chemistry

    Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bilirubin (Total), Calcium, Creatinine, Creatinine clearance, Lactate dehydrogenase, Potassium, Sodium and Urea

    Time frame: Assessed at screening, pre-dose, 24 h and 48 h post-dose and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2

40. Haematology

    Basophils, Eosinophils, Haematocrit, Haemoglobin, Lymphocytes, MCH, MCHC, MCV, Monocytes, Neutrophils, Red Blood Cell Count, White Blood Cell Count and Thrombocytes

    Time frame: Assessed at screening, pre-dose, 24 h and 48 h post-dose and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2

41. Urinalysis

    Leucocytes, protein, erythrocytes, glucose and specific gravity

    Time frame: Assessed at screening, pre-dose, 24 h and 48 h post-dose and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2

Publications

• Zurth C, Nykanen P, Wilkinson G, Taavitsainen P, Vuorela A, Huang F, Reschke S, Koskinen M. Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment. Clin Pharmacokinet. 2022 Apr;61(4):565-575. doi: 10.1007/s40262-021-01078-y. Epub 2021 Dec 6. PubMed 34866168 ↗