Primary objectives:To determine the mass balance of drug-related radioactivity following i.v. administration of a single dose of [14C]-OTL0038 in humans.To determine the primary route and mechanism of excretion of drug-related radioactivity…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
imaging agent for overian cancer
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Radioactivity and Pharmacokinetic Parameters
Total radioactivity and PK parameters will be derived by non-compartmental
analysis from total radioactivity-time as well as unchanged parent drug-time
profiles.
Safety and Tolerability Parameters
Baseline is defined as the last available and evaluable value measured prior to
[14C]-OTL0038 administration (vital signs, ECG, laboratory parameters), unless
otherwise specified.
The following are defined as safety/tolerability parameters:
Adverse events
Vital signs
12-lead ECG
Clinical laboratory parameters
Local tolerability
Weight
Physical examination
Calculation of Mass Balance
Individual plasma and whole blood total radioactivity as well as unchanged
parent drug (LC-MS/MS) data will be used to directly obtain Cmax and tmax,
respectively.
Mass balance will be calculated as the percent of total administered
radioactivity recovered in urine and feces. To calculate mass balance, the
amount of administered radioactivity is defined as the total radioactivity in
the dosing solution minus any radioactivity loss due to adsorption to the
infusion bag, etc.
The PK parameters on total radioactivity as well as unchanged parent drug
(LC-MS/MS) data in plasma and whole blood will be based on actual blood
sampling times [h] (relative to the corresponding administration time) rounded
to two digits and negative pre-dose times will be set to zero.
Secondary outcome
Vital signs values;
Clinical laboratory values;
Number of subjects with adverse events (AEs);
12-lead ECG values.
Local tolerance
Weight
Physical examination outcomes.
Background summary
On Target Laboratories has developed OTL38, a folate analog conjugated with an
indole cyanine green dye as a tumor-specific imaging agent. OTL38 binds
specifically to the high affinity FR and functions as an imaging agent in
patients with tumors that overexpress FRα. Following i.v. infusion of OTL38,
the agent distributes throughout the body and is rapidly cleared from the
circulation, while areas with a high concentration of folate receptors, such as
several carcinomas, retain the agent. When OTL38 is excited by light between
the wavelengths of 760-776 nm (maximum excitation at 774-776 nm), it emits
light (fluoresces) at wavelengths in the near-infrared (NIR) spectrum (maximum
emission 794-796 nm). This fluorescence of the malignant tissue is captured by
an imaging system that can be used by the surgeon, along with normal
perioperative procedures such as palpation and visual observation, to decide
which tissues to remove during cytoreduction surgery.
OTL38 is currently in clinical stage development for both ovarian cancer (phase
3) and lung cancer (phase 2). A complete overview of all pre-clinical and
clinical studies conducted with OTL38 can be found in the Investigator*s
Brochure.
Study objective
Primary objectives:
To determine the mass balance of drug-related radioactivity following i.v.
administration of a single dose of [14C]-OTL0038 in humans.
To determine the primary route and mechanism of excretion of drug-related
radioactivity following intravenous administration of a single dose of
[14C]-OTL0038 in humans.
To estimate the plasma exposure of metabolite(s) as a percentage of total
drug-related exposure.
Profiling of [14C]-OTL0038 metabolites in blood, urine and feces.
Secondary objective:
To evaluate the safety and tolerability of [14C]-OTL0038 after a single
intravenous dose.
Study design
The present study is designed to investigate the absorption, metabolism, and
excretion of OTL0038 as well as the safety/tolerability of OTL0038 following
the administration of a single i.v. dose to healthy subjects.
Intervention
Up to 8 healthy male subjects will receive a single 60 minute i.v. infusion of
1.75 mg [14C]-OTL0038 containing approximately 105 µCi radioactivity.
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IMPD for further information.
Win Hentschel Blvd. 1281
West Lafayette IN47906
US
Win Hentschel Blvd. 1281
West Lafayette IN47906
US
Listed location countries
Age
Inclusion criteria
1. Able to provide informed consent to participate in this study after reading
the participant information sheet and informed consent form and after having
the opportunity to discuss the study with the Investigator or designee.
2. Healthy and free from clinically significant illness or disease as
determined by medical history, physical examination, laboratory and other tests
at Screening.
3. Male Caucasian subjects, aged 18 to 60 years (inclusive) at Screening.
Exclusion criteria
1. Any finding of the medical examination (including blood pressure, pulse rate
and ECG) deviating from normal and of clinical relevance.
2. History or current clinically significant gastrointestinal, hepatic, renal,
respiratory, cardiovascular, metabolic, immunologic, hormonal disorders.
3. History of any major surgery within the last 4 weeks before Screening or any
bone fracture within the last 2 months before Screening.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002985-10-NL |
| CCMO | NL70868.056.19 |