A study designed to investigate how radiolabelled RPC1063 is taken up, broken down and removed from the body

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2016-003073-18-GB
• Date of registration: 16/09/2016
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl
• Public title: A study designed to investigate how radiolabelled RPC1063 is taken up, broken down and removed from the body
• Scientific title: A Phase I, Single-Centre, Single Dose Oral Excretion Balance Study of [14C]-RPC1063 in Healthy Male Adults - ADME study of [14C]-RPC1063 in healthy male subjects (QCL117686)
• Date of first enrolment: 29/09/2016
• Target sample size: 6
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003073-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Study Director
• Affiliation: Receptos Services LLC, a wholly owned subsidiary of Celgene Corporation

• Name: Study Director
• Affiliation: Receptos Services LLC, a wholly owned subsidiary of Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1.Subject is male
2.Subject is 30 to 65 years of age
3.Subject has a body weight of at least 50 kg; body mass index (BMI) of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
4.Subject is willing and able to communicate and participate in the whole study
5.Subject has regular bowel movements (average stool production =1 and =3 stools per day)
6.Subject has suitable veins for multiple cannulation as assessed by the investigator at screening
7.Subject is able to comprehend the informed consent form, provide written informed consent, and able to comply with requirements of the study.
8.Subject agrees to use an adequate method of contraception

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
1.Subject has received any IMP in a clinical research study within the previous 3 months
2.Subject is a study site employee or an immediate family member of a study site or sponsor employee
3.Subject has a history of any drug or alcohol abuse in the past 2 years
4.Subject has regular alcohol consumption of >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
5.Subject is a current smoker or has smoked within the last 12 months; including cigarettes, e-cigarettes and nicotine replacement products. Positive cotinine test result at screening and each admission
6.Subject has radiation exposure, 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
7.Subjects has been enrolled in an ADME study in the last 12 months
8.Subject has clinically significant abnormal biochemistry or haematology as judged by the investigator
9.Subject has positive drugs of abuse test result
10.Subject has positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
11.Subject has evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <90 mL/min using the Cockcroft-Gault equation
12.Subject has ALT or AST concentration >1.25 × the upper limit of normal at screening
13.Subject has history of cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease as judged by the investigator
14.Subject has had serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
15.Subject has presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active
16.Subject has donated or lost greater than 400 mL of blood within the previous 3 months
17.Subject is taking, or has taken, any prescribed or over-the-counter drug (other than 2 g per 24 h paracetamol) dietary or herbal remedies within 14 days before IMP administration, or has taken St. John’s wort within 28 days before IMP administration. 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.
18.Subject fails to satisfy the investigator of fitness to participate for any other reason



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

The drug is a potential treatment for adult patients with relapsing multiple sclerosis (RMS) and for adult patients with moderately to severely active inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD).
MedDRA version: 19.0 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
MedDRA version: 19.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: [14C]-RPC1063 Solution (0.1 mg/mL) for Oral Administration
Pharmaceutical Form: Oral solution
INN or Proposed INN: Ozanimod hydrochloride
CAS Number: 1618636-37-5
Current Sponsor code: RPC1063HCL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.1-

Primary Outcome(s)

Primary end point(s): The primary endpoints for the study are:
•Determination of routes and rates of elimination of [14C]-RPC1063 by assessment of Ae total radioactivity and %Ae total radioactivity, Cum Ae (total), Cum %Ae (total) for urine and faeces, PK profile of total radioactivity and parent in plasma
•Mass balance recovery of total radioactivity in urine, faeces and all excreta: amount excreted (Ae) and Ae as a percentage of the administered dose (%Ae), cumulative recovery (Cum Ae) and cumulative recovery expressed as a percentage of the dose (Cum %Ae)

Timepoint(s) of evaluation of this end point: Plasma samples will be collected for analysis at predose, at specified intervals postdose.
Urine samples will be collected at predose, then at 0 to 6h, 6 to 12h, 12 to 24h post dose and then every 24 hours until the end of the study.
Faecal samples will be collected at predose, then every 24 hours until 168 hours post dose.

Main Objective: The primary objectives of the study are:

•To determine how the drug [14C]-RPC1063 moves through the body and how fast it is removed from the body
•To assess the amount of radioactivity found in blood, urine and faecal samples after a single dose of [14C]-RPC1063

Secondary Objective: The secondary objectives of the study are:

•To provide blood, urine and faecal samples to look at the breakdown products and to find out the structure of these products
•To identify the chemical structure of each breakdown product which is more than 10% of circulating total radioactivity
•To look at the pharmacokinetics of [14C]-RPC1063 when given by mouth (pharmacokinetics is the impact of the body on the drug)
•To look at how much radioactivity is found in the blood cells
•To provide additional safety and tolerability information for RPC1063 (Ozanimod)

Secondary Outcome(s)

Secondary end point(s): Collection of plasma, urine and faeces for metabolite profiling and structural identification
Determination of the chemical structure of the “major” metabolites of [14C]-RPC1063
Assessment of the oral PK of a solution formulation of [14C]-RPC1063 by calculation of the following parameters for ozanimod and its metabolites RP101988, RP101075, RP101124 and RP101442: Tmax, Cmax, AUC0-last, AUC0-inf, ?z, t1/2, CL/F, Vz/F, CLr, Ae
Evaluation of whole blood:plasma concentration ratios for total radioactivity
To collect additional information on the safety and tolerability of ozanimod by assessing: physical examination, safety laboratory tests, vital signs, electrocardiograms (ECGs) and AEs

Timepoint(s) of evaluation of this end point: Plasma, urine and faeces will be collected as described in section E5-1 for metabolite profiling, structural identification and assessment of the PK following oral administration.

Blood samples for total radioactivity will be taken pre-dose, at 1, 6, 24 and 48 hrs after dosing

Safety and tolerability will be collected throughout study.

Secondary ID(s)

RPC01-1909

Source(s) of Monetary Support

Celgene International II Sàrl

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 07/12/2017
• Date Completed: 21/11/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-003073-18/results