Debio-0932 is currently under development for the treatment of cancer. MedDRA version: 14.1 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: 250 mg Debio 0932 oral immediate release tablet
Pharmaceutical Form: Tablet
Current Sponsor code: DEBIO 0932
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration
Sponsors
Debiopharm SA
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Healthy males 2. Part 1: Age 18 to 65 years of age; Part 2: Age 30 to 65 years of age 3. Body mass index of 18 to 32 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 5. Must provide written informed consent 6. Must agree to use an adequate method of contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
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 >21 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. Radiation exposure from clinical studies, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study 8. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening 9. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator 10. Clinically significant vital signs or ECG values as judged by the investigator 11. Positive drugs of abuse test result 12. Positive hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) results 13. History of clinically significant cardiovascular, renal, hepatic, respiratory or gastrointestinal disease as judged by the investigator 14. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 15. Presence or history of allergy requiring treatment. Hayfever is allowed unless it is active 16. Donation or loss of greater than 400 mL of blood within the previous 3 months 17. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IMP administration or within 5 half-lives of the drug, whichever is longer unless not considered to interfere with the objectives of the study as judged by both the PI and sponsor’s medical monitor 18. Concomitant treatment with any drug on the prohibited medication list (provided separately) 19. Failure to satisfy the investigator of fitness to participate for any other reason
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of Part 1 of the study is: • To determine the absolute oral bioavailability at 2 dose levels of Debio 0932 in healthy male subjects The primary objectives of Part 2 of the study are: • To assess the mass balance recovery of total radioactivity from excreta in healthy subjects after oral administration of [14C]-Debio 0932 • To determine the metabolic profile of [14C]-Debio 0932 in plasma, urine and faeces following oral administration ;Secondary Objective: •To determine the PK of total radioactivity, [14C]-Debio 0932 and [14C] Debio 0932 MET1 following IV) and oral admin of [14C]-Debio 0932 in healthy subjects and the Pk ofDebio 0932/Debio 0932 MET1 following admin of Debio 0932 •To explore elimination of total radioactivity, [14C]-Debio 0932 and [14C]-Debio 0932-MET1 following IV and oral admin of [14C]-Debio 0932 in healthy subjects •To explore the elimination of Debio 0932 and Debio 0932-MET1 in urine following oral administration of Debio 0932 in healthy subjects •To provide safety and tolerability information of Debio 0932 in healthy subjects •To collect pharmacogenetic data to explore whether they may affect the PK of Debio 0932 •To determine the chemical structure of “major” metabolites of [14C]-Debio 0932 •To evaluate the blood to plasma ratio of total radioactivity, [14C]-Debio 0932 and [14C] Debio 0932 MET1 •To determine the ex vivo protein binding for total radioactivity, [14C]-Debio 0932 and [14C]-Debio 0932-MET1 ;Primary end point(s): The primary endpoint for Part 1 is the absolute bioavailability (F) of 250 mg and 500 mg Debio 0932 based on AUC8. The primary endpoints for Part 2 are: • Mass balance recovery of total radioactivity in urine, faeces and expired air (Ae, Af, Aa, At, Fe, Ff, Fa and Ft) • Radiochromatographic characterisation of the metabolite profile of metabolites of [14C] Debio 0932 in plasma, urine and faeces ;Timepoint(s) of evaluation of this end point: Part 1: Urine: 0-48 hr post-dose Faeces: | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints for Part 1 of the study are: • Determination of the PK profile of total radioactivity, [14C]-Debio 0932 and [14C] Debio 0932-MET1 following an IV microtracer dose of [14C]-Debio 0932 (Tlag, Tmax, Cmax, C24, AUC(0-last), AUC8, AUC%extrap, ?z, T1/2, MRT, Cl, Vd and CLr). • Determination of the PK profile of Debio 0932 and Debio 0932-MET1 following oral administration of Debio 0932 (Tlag, Tmax, Cmax, AUC(0-last), AUC8, AUC%extrap, ?z, T1/2, MRT [Debio 0932 only], CL/F, Vz/F and CLr). • Recovery of total radioactivity, and if possible, [14C]-Debio 0932 and [14C]-Debio 0932-MET1 in urine, faeces and overall (Ae, Af, At, Fe, Ff and Ft) • Recovery of Debio 0932 and Debio 0932-MET1 in urine will be be also compared (Ae and Fe) • Collection of further information about the safety and tolerability of Debio 0932 by assessing physical examinations, safety laboratory tests, vital signs, ECGs and AEs. • To collect pharmacogenetic data related to cytochromes and other metabolic enzymes/transporters involved in the metabolism and mechanism of action of Debio 0932 The secondary endpoints of Part 2 of the study are: • Determination of the PK profile of total radioactivity, Debio 0932 and Debio 0932 MET1 following oral administration of Debio 0932 (Tlag, Tmax, Cmax, AUC(0-last), AUC8, AUC%extrap, ?z, T1/2 and MRT (total radioactivity and Debio 0932). F will also be determined for total radioactivity and Debio 0932 only using the mean IV data obtained from Part 1). • Recovery of [14C]-Debio 0932 and [14C] Debio 0932 MET1 in urine, faeces and overall (Ae, Af, At Fe, Ff and Ft). • Determination of a chemical structure of major metabolites of [14C] Debio 0932. • Evaluation of the whole blood:plasma concentration ratios of total radioactivity, [14C]-Debio 0932 and [14C]-Debio 0932-MET1. • Selected plasma samples will be analysed for protein binding of total radioactivity, [14C]-Debio 0932 and [14C]-Debio 0932-MET1. • Collection | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trial Management
Debiopharm SA
Outcome results
None listed