Clinical trial NCT03484585: Rogaratinib (BAY1163877) Human Mass Balance Study
Official title: Single Center, Open-label, Non-randomized, Non-placebo-controlled Study to Investigate the Metabolism, Excretion Pattern, Mass Balance, Safety, Tolerability and Pharmacokinetics After Single Administration of 200 mg [14C]Rogaratinib (Oral Solution) in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clinical Trial, Phase I
Pharmacokinetics
Keywords: Mass Balance, metabolism and excretion pattern
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-04-02
Enrollment: 6
Sex: MALE
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine the mass balance and routes of excretion of total radioactivity after a single oral 200 mg dose of \[14C\]rogaratinib given as a solution. For further clinical development, human mass balance data are required to elucidate the absorption, distribution, metabolism, and excretion (ADME) of rogaratinib.


Eligibility criteria: Inclusion Criteria:

* The written informed consent must be signed before any study specific tests or procedures are done
* Age: 21 to 65 years (inclusive) at the first screening examination visit
* Body mass index (BMI) 18.5 to 32.0 kg/m2 (both inclusive) and a total body weight of 55 to 100 kg (both inclusive)
* Healthy male subject, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, laboratory tests, physical, cardiac and full ophthalmologic examination
* Subjects of reproductive potential with a partner of child-bearing potential must agree to use adequate contraception when sexually active. This applies from signing of the ICF until 3 months after the study drug administration. The definition of adequate contraception will be based on the judgment of the investigator and on local requirements. Acceptable methods of contraception include, but are not limited to, (i) condoms (male or female, should not be used together) with or without a spermicidal agent; (ii) diaphragm or cervical cap with spermicide; (iii) intra-uterine device; (iv) hormone-based contraception. Subjects must agree to utilize two reliable and acceptable methods of contraception simultaneously. This is not required if safe contraception is achieved by a permanent method, such as vasectomy of the subject or bilateral fallopian tube blockage of the subject's partner; OR if the subject has no requirement for contraception (e.g. same sex partners).
* Ability to understand and follow study-related instructions

Key Exclusion Criteria:

* Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
* Known or suspected hypersensitivity to rogaratinib or to excipients in the formulation, or to any FGFR inhibitor
* Known severe allergies, non-allergic drug reactions, or multiple drug allergies
* Relevant diseases within the last 4 weeks prior to the first study drug administration
* Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
* Presence of high myopia or pathological myopia (defined as spherical equivalent ≥ 6.00D), or any retinal abnormalities consistent with pathologic myopia
* Known recent use of recreational drugs (last 3 months), suspicion of drug or alcohol abuse, or positive results of the urine drug or alcohol screen at screening or baseline
* Use of any medication within 14 days before administration of the study drug except paracetamol
* Smoking more than 5 cigarettes daily
* Exposure to radiation for diagnostic reasons (except dental X rays and plain X rays of thorax and bony skeleton \[excluding spinal column\]), during work or during participation in a clinical study in the period of 1 year prior to screening
* Participation in another study with a radiation burden of \> 0.1 mSv and ≤ 1 mSv in the period of 1 year prior to screening; a radiation burden of \> 1.1 mSv and ≤ 2 mSv in the period of 2 years prior to screening; a radiation burden of \> 2.1 mSv and ≤ 3 mSv in the period of 3 years prior to screening, etc (add 1 year per 1 mSv)
* Previous (within the preceding 3 months; end of previous study to first treatment of the current study) or concomitant participation in another clinical study with investigational medicinal product(s)

Primary outcomes:
measure: Cmax of rogaratinib in plasma
timeFrame: At pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h post-dose. Collection will be extended depending on the radioactivity recovery.
measure: AUC(0-tlast) of rogaratinib in plasma
timeFrame: At pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h post-dose. Collection will be extended depending on the radioactivity recovery.
measure: AUC of rogaratinib in plasma
timeFrame: At pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h post-dose. Collection will be extended depending on the radioactivity recovery.
measure: Cmax of total radioactivity in plasma and whole blood
timeFrame: At pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h post-dose. Collection will be extended depending on the radioactivity recovery.
measure: AUC(0-tlast) of total radioactivity in plasma and whole blood
timeFrame: At pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h post-dose. Collection will be extended depending on the radioactivity recovery.
measure: AUC of total radioactivity in plasma and whole blood
timeFrame: At pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 h post-dose. Collection will be extended depending on the radioactivity recovery.
measure: AE,ur (%) of rogaratinib and its metabolites
timeFrame: In intervals of 12h from Day -1 till Day 2 and in intervals of 24h afterwards: at pre-dose (-12-0h), 0-12, 12-24, 24-48, 48-72, 72-96,96-120, 120-144 and 144-168 hours post dose. Collection will be extended depending on the radioactivity recovery.
measure: AE,fec (%) of rogaratinib and its metabolites
timeFrame: In intervals of 24h at pre dose (-18-0h), 0-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours post dose. Collection will be extended depending on the radioactivity recovery.
measure: AE,vom (%) of rogaratinib and its metabolites, if applicable
timeFrame: During the first 6 hours after dosing
Secondary outcomes:
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRAHealthSciences
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: