- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03368846
Open, Single-dose/-Period Study to Assess Mass Balance Recovery, Metabolite Profile/Identification of 14C-Varlitinib
September 10, 2018 updated by: ASLAN Pharmaceuticals
An Open Label, Single-dose, Single-period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-Varlitinib in Healthy Male Subjects
This is a single-centre, open-label, non-randomised, single oral dose study in healthy male subjects. It is planned to enrol a single cohort of 6 healthy male subjects to ensure data in 4 evaluable subjects.
Each subject will receive a single administration of 120 mg [14C] varlitinib oral suspension containing not more than (NMT) 2.9 MBq (79 µCi), in the fed state.
Study Overview
Detailed Description
Subjects will be screened for eligibility to participate in the study up to 28 days before dosing.
Subjects will be admitted to the clinical unit on the evening prior to IMP administration (Day 1) and will fast overnight for a minimum of 8 h.
Subjects will be dosed on the morning of Day 1 following a light breakfast, and will remain resident in the clinic until up to 240 h after dosing (Day 11).
It is planned that subjects will be released as a group when all subjects have achieved a mass balance cumulative recovery of >90%, or if <1% of the dose administered has been collected in urine and faeces within 2 separate, consecutive 24 h periods.
In this case, collection of all samples (blood, urine and faeces) will cease and the subjects will undergo discharge assessments.
If this criterion has not been met by all subjects on Day 11, the residency period may be extended by a further 48 h maximum (up to Day 13).
If the criterion is still not met by Day 13, or if additional residency is not considered appropriate or necessary, then home collections of urine and/or faeces may be requested at the discretion of the investigator for individual subjects.
Study Type
Interventional
Enrollment (Actual)
6
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Nottingham, United Kingdom
- Quotient Clinical LTD
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
30 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Healthy males of non-Asian descent
- Aged 30 to 65 years
- Body mass index of 18.0 to 35.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
- Must be willing and able to communicate and participate in the whole study
- Must provide written informed consent
- Must agree to use an adequate method of contraception (as defined in Section 9.4)
- Must have regular bowel movements (ie, average stool production of ≥1 and ≤3 stools per day)
- Subject is considered healthy on the basis of medical history, physical examination, ECG, vital signs and clinical laboratory assessments.
Exclusion Criteria:
- Subjects who have received any IMP in a clinical research study within the previous 3 months
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- Subjects with pregnant partners
- Subjects who have previously been enrolled in this study
- History of any drug or alcohol abuse in the past 2 years
- Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
- Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission
- Users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
- 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
- Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
- Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1)
- Neutrophil count <1.8 x109/L at screening
- ALT and AST >1.25 x upper limit of normal range at screening
- QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 msec at screening
- Positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1)
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
- Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <80 mL/min using the Cockcroft-Gault equation
- History of clinically relevant cardiovascular, renal, hepatic, chronic respiratory or Gl disease, neurological or psychiatric disorder, as judged by the investigator
- History of clinically relevant dermatological disease (eg eczema, psoriasis, drug rashes) or the presence of dermatological conditions at screening (eg acne, eczema, dermatitis etc)
- Subjects with a history of cholecystectomy or gall stones
- Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
- Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active
- Donation or loss of greater than 400 mL of blood within the previous 3 months
- Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies in the 14 days before IMP administration; with the exception of 4 g per day paracetamol [see Section 11.4]). Further 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.
- Failure to satisfy the investigator of fitness to participate for any other reason
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: [14C]-Varlitinib
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[14C]-Varlitinib
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mass balance recovery after a single oral dose of [14C] varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
Mass balance recovery of [14C] varlitinib recovered in urine, faeces, and all excreta
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Assessments will be made up to 13 days postdose
|
Metabolite profiling and structural identification of metabolites in plasma, urine and faeces
Time Frame: Assessments will be made up to 13 days postdose
|
Identification of the chemical structure of metabolites
|
Assessments will be made up to 13 days postdose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Routes and rates of elimination of [14C] varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
Amount [14C] varlitinib excreted for urine and faeces
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Assessments will be made up to 13 days postdose
|
Determination of the chemical structure of the "major" metabolites of [14C] varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
Identification of the chemical structure of each metabolite accounting for greater than 10%
|
Assessments will be made up to 13 days postdose
|
Evaluation of whole blood:plasma concentration ratios for total radioactivity
Time Frame: Assessments will be made up to 13 days postdose
|
Assessments will be made up to 13 days postdose
|
|
PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
Peak Plasma Concentration (Cmax)
|
Assessments will be made up to 13 days postdose
|
PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
Area under the plasma concentration versus time curve (AUC)
|
Assessments will be made up to 13 days postdose
|
PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
Half life
|
Assessments will be made up to 13 days postdose
|
PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
The time from dosing at which Cmax was apparent
|
Assessments will be made up to 13 days postdose
|
Collect additional information on the safety and tolerability of varlitinib
Time Frame: Assessments will be made up to 13 days postdose
|
Number of participants with abnormal laboratory values and/or adverse events
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Assessments will be made up to 13 days postdose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 23, 2017
Primary Completion (Actual)
December 6, 2017
Study Completion (Actual)
December 14, 2017
Study Registration Dates
First Submitted
November 22, 2017
First Submitted That Met QC Criteria
December 5, 2017
First Posted (Actual)
December 11, 2017
Study Record Updates
Last Update Posted (Actual)
September 11, 2018
Last Update Submitted That Met QC Criteria
September 10, 2018
Last Verified
September 1, 2018
More Information
Terms related to this study
Other Study ID Numbers
- ASLAN001-018
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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