Primary ObjectiveTo assess the tolerability and safety of single ascending oral doses of PHA-022121 administered after a standard meal and of a single 40 mg dose under fasted conditions in healthy adult subjects.To assess the PK characteristics of…
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints:
Primary endpoint, safety:
All standard safety assessments including physical examination, vital signs,
adverse events, hematology, chemistry, urinalysis and ECG.
Primary endpoint, pharmacokinetics:
Plasma PK parameters tmax, Cmax, AUC0-12h, AUC0-24h, AUClast, AUCinf, t1/2,
CL/F and Vz/F of PHA-022121.
Secondary outcome
Plasma PK parameters tmax, Cmax, AUC0-12h, AUC0-24h, AUClast, AUCinf, and t1/2,
of the major metabolite M2-D.
QT, and the heart rate-corrected QT interval by Fridericia*s formula (QTcF)
Background summary
An oral treatment for HAE attacks is currently not available rendering the
management of this disease difficult: all of the currently approved drugs for
HAE, except for androgens, can only be applied by i.v. or sc route, which is
often associated with a delay of drug administration, discomforts, local side
effects and with a reduction in the QoL for the patients. Therefore, there is a
strong unmet medical need for an efficacious orally bioavailable drug for the
treatment and/or prevention of acute HAE attacks.
Of all products available to patients or in development, only one other
antagonizes the B2 receptor, namely icatibant. Extensive clinical experience
has demonstrated the selectivity, safety, and rapid onset of action of this
mechanism to resolve HAE attacks of all causes. PHA-022121 retains these
characteristics through the shared mechanism, as demonstrated preclinically in
the BK challenge model adapted from human clinical experience to monkey.
Study objective
Primary Objective
To assess the tolerability and safety of single ascending oral doses of
PHA-022121 administered after a standard meal and of a single 40 mg dose under
fasted conditions in healthy adult subjects.
To assess the PK characteristics of PHA-022121 after administration of single
ascending oral doses.
Secondary Objectives
To assess the PK characteristics of the major active metabolite M2-D after
administration of single ascending doses of PHA-022121.
To assess the concentration-QTc effect of PHA-022121 after single ascending
doses.
Study design
This is a randomized, double-blind, placebo-controlled study for PHA 022121 and
will be conducted in healthy subjects at a single study center.
This study is an extension of the SAD range of PHA-022121 as studied in trial
PHA022121-C001 by four sequential cohorts. Within each cohort, 8 subjects will
be randomized to PHA-022121 (N = 6) and to matching placebo (N = 2).
Accordingly, up to 32 subjects will be enrolled in this study. Each cohort must
comprise at least 3 female subjects.
After each cohort, safety and PK data will be available and submitted to the
Safety Monitoring Committee (SMC) and Ethics Committee (EC), which will decide
on predefined safety and PK decision criteria whether the next higher single
dose can be administered.
Intervention
PHA-022121 will be made available as an oral self-micro emulsifying drug
delivery system (SMEDDS) solution containing 50 mg/mL PHA-022121.
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IB for further
information.
Leiden Bio Science Park, J.H. Oortweg 21
Leiden 2333 CH
NL
Leiden Bio Science Park, J.H. Oortweg 21
Leiden 2333 CH
NL
Listed location countries
Age
Inclusion criteria
Healthy male and female subjects of non-childbearing potential.
Between 18 and 65 years of age, inclusive.
Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive).
Healthy on the basis of physical examination, medical history, vital signs,
clinical laboratory tests, and 12-lead ECG performed at screening. If any of
the results are abnormal, the subject may be included only if the investigator
judges that the abnormalities or deviations from normal are not clinically
significant. This determination must be recorded in the subject's source
documents and initialled by the investigator.
A resting heart/pulse rate (supine position for 5 minutes) between 40 and 100
beats per minute (bpm). If heart/pulse rate is out of range, up to 2 repeated
assessments are permitted.
A resting blood pressure (supine position for 5 minutes) between 90 and 140
mmHg systolic, inclusive, and between 40 to 90 mmHg diastolic. If blood
pressure requirements are out of range, up to 2 repeated assessments are
permitted.
Exclusion criteria
Clinically relevant allergy (except for untreated, asymptomatic, seasonal
allergies at time of dosing) or drug hypersensitivity.
Known hypersensitivity to the drug substance, or any inactive ingredient(s) of
the investigational product (refer to investigator's brochure).
History of any medical condition or prior surgery of the GI-tract that could
alter the absorption of orally administered drugs (does not apply to history of
appendectomy).
History or current evidence of any form of angioedema.
History or current evidence of any form of bronchial asthma.
Design
Recruitment
Medical products/devices used
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 | EUCTR2020-002013-18-NL |
| CCMO | NL73764.056.20 |