The purpose of this study is to investigate how quickly and to what extent the new compound PL8177 is absorbed and eliminated from the body (this is called pharmacokinetics) when it is administered to healthy volunteers. PL8177 will be labelled with…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate release of [14C]-PL8177 from the polymer-bound form of [14C]
PL8177 in the colon after oral administration. This will be accomplished by
observation of the formation of metabolite PL8435.
To confirm that the orally administered, polymer-bound form of [14C] PL8177
does not result in systemic exposure to [14C]-PL8177 and/or metabolite
[14C]-PL8435 (in healthy male subjects).
To establish the relationship between an oral dose of polymer-bound [14C]
PL8177 and the amount of [14C] PL8177 and/or metabolite [14C]-PL8435 in the
colon.
Secondary outcome
To evaluate the safety and tolerability of the orally administered,
polymer-bound form of [14C] PL8177 in healthy male subjects.
Background summary
PL8177 is a new compound that may eventually be used for the treatment of
ulcerative colitis. Ulcerative colitis is an inflammatory bowel disease. It is
characterized by abdominal pain, persistent diarrhea and loss of appetite. The
compound PL8177 is a protein-like structure with anti-inflammatory properties
as shown in studies with animals. PL8177 has recently been administered to
humans via an injection under the skin (subcutaneous) to investigate how safe
it is and how well it is tolerated. The Sponsor has now developed a capsule of
PL8177 that can be orally administered and would thus facilitate the
administration of the compound. PL8177 in capsule format is formulated in such
a way that it should exclusively reach the site where action takes place, i.e.,
the colon (large intestine) and not reach the circulation. This will be
assessed in this study.
In addition to the study compound, also a strong laxative will be administered
in this study. This laxative will be given at different time points after
administration of the study compound. The laxative is used to remove the
contents of the colon in order to examine the level of PL8177 at certain
specific time points. Without the laxative, the timing of naturally occurring
defecation is highly variable. The highly variable aspect of natural defecation
makes it difficult to study how much and also when PL8177 reaches the colon. In
addition, PL8177 degrades in feces which complicates measurement of how much
study compound actually reached the colon.
Study objective
The purpose of this study is to investigate how quickly and to what extent the
new compound PL8177 is absorbed and eliminated from the body (this is called
pharmacokinetics) when it is administered to healthy volunteers. PL8177 will be
labelled with 14 Carbon (14C) and is thus radioactive. In this way PL8177 can
be traced in blood, urine and feces. The additional radiation the volunteer
will be exposed to in this study is negligible (that is, it is less than the
natural background radiation during 1 month). It will also be investigated how
safe PL8177 is and how well it is tolerated.
Study design
The actual study will consist of 1 period during which the subject will stay in
the research center for 5 days (4 nights) if he participates in Groups 1 to 5,
or for 7 days (6 nights) if he participates in Group 6.
Day 1 is the day of administration of the study compound. The subject is
expected at the research center at 14:00 h in the afternoon prior to the day of
administration of the study compound (so on Day -1). He will leave the research
center on Day 4 (Groups 1 to 5) or Day 6 (Group 6) of the study, depending on
the group he is in.
The subject will receive a single dose of 70 microgram (µg)/33.3 kBq
radiolabeled PL8177 as an oral capsule with 240 milliliters (mL) of (tap) water
on Day 1. In addition to the study compound, volunteers in Groups 1 to 5 will
receive a strong laxative and volunteers in Group 6 will not receive any
laxative.
Intervention
The subject will receive a single dose of 70 microgram (µg)/33.3 kBq
radiolabeled PL8177 as an oral capsule with 240 milliliters (mL) of (tap) water
on Day 1. In addition to the study compound, volunteers in Groups 1 to 5 will
receive a strong laxative and volunteers in Group 6 will not receive any
laxative.
Study burden and risks
Disadvantages of participation in the study may be:
• possible side effects
• possible discomforts of the evaluations in the study
Participation in the study also means:
• time requirements
• tests you will have to do
• instructions you need to follow
Drawing blood and/or insertion of the indwelling cannula (tube in an arm vein)
may be painful or cause some bruising.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on your arms and legs. Prolonged use of these electrodes can
cause skin irritation (rash and itching).
In this study radiolabeled PL8177 will be used. The amount of radioactivity in
this dose will be approximately 18.5 kBq (kBq=kiloBecquerel, this is a unit to
express the amount of radioactivity in the study compound). The average
environmental background radiation in The Netherlands is approximately 2.5 mSv
per year (mSv=miliSievert, this is the unit which indicates the burden on the
human body thus the effect on the human body of the amount of radioactivity
administered). The additional radiation you will be exposed to in this study is
negligible (that is, it is less than the natural background radiation during 1
month).
Cedar Brook Drive 4B
Cranbury NJ 08512
US
Cedar Brook Drive 4B
Cranbury NJ 08512
US
Listed location countries
Age
Inclusion criteria
1.Males of any race, between 18 and 55 years of age, inclusive, at screening. ;2.Body mass index between 18.0 and 30.0 kg/m2, inclusive, at screening.;3.In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert*s syndrome] is not acceptable) at screening or admission (Day -1) as assessed by the Investigator (or designee).;4.Blood pressure at screening must be within the following ranges (measured with subjects in the supine position after they have rested for at least 5 minutes): systolic blood pressure >=90 and <=139 mmHg and diastolic blood pressure >=45 and <=89 mmHg. If blood pressure readings are out of range, the Investigator (or designee) may obtain 1 additional reading, so that up to 2 consecutive assessments are made within 1 hour.
Exclusion criteria
1. Employee of PRA or the Sponsor.
2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
3. History of irritable bowel syndrome, Crohn*s disease, or ulcerative colitis.
4. History of chronic constipation.
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 | EUCTR201800249541-NL |
| CCMO | NL67194.056.18 |