- To compare the pharmacokinetics (PK) of glepaglutide after a single subcutaneous (SC) administration by vial/syringe and by autoinjector.- To evaluate the safety and tolerability of glepaglutide following SC dosing in healthy subjects.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Bioequivalence
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Cmax = maximum concentration of ZP1848total in plasma
• AUC0-t = area under the plasma ZP1848total concentration-time curve (AUC)
from time zero to the last time point with a measurable concentration both for
the conceptual analyte ZP1848total (glepaglutide + ZP18481-34 + ZP18481-35) in
plasma
Secondary outcome
• AUC0-inf = AUC from time 0 extrapolated to infinity
• AUC0-t = AUC from time 0 to the last time point with a measurable
concentration in plasma for ZP1848 and main metabolite ZP18481-34
• Cmax = maximum concentration of ZP1848 and ZP18481 34 in plasma
• Tmax = time to attain Cmax
• *z = terminal elimination phase rate constant
• t1/2 = terminal elimination half-life all for the conceptual analyte
ZP1848total and main metabolite ZP18481 34 in plasma
• Adverse events
Safety:
• Change from baseline in:
o Clinical laboratory values (hematology, clinical chemistry, and urinalysis)
o Standard 12-lead electrocardiogram (ECG) evaluation
o Vital signs (diastolic and systolic blood pressure, heart rate, and body
temperature)
o Physical examination evaluation
Immunogenicity
• Overall anti-glepaglutide antibody incidences (treatment-induced and
treatment-boosted) and titers
• Antibodies reacting to the main metabolite (ZP18481-34)
• Antibodies cross-reacting to endogenous GLP-2
• Glepaglutide neutralizing antibodies
Background summary
Glepaglutide is a new compound that may be used for the treatment of short
bowel syndrome. Short bowel syndrome is a disease where there is a shortage of
functional small intestine, for example due to disease or surgery. As patients
that suffer from this syndrome cannot effectively absorb fluid and nutrients
from food, it often results in symptoms such as feeling tired, weight loss,
dehydration, and malnutrition.
A compound that is present in the intestines (GLP-2) has been found to be able
to improve the functioning of the intestines and could increase the absorption
of nutrients. The downside of GLP-2 is that it is quickly degraded in the body.
Glepaglutide is a new compound that looks the same as GLP-2, but works for a
longer period.
Study objective
- To compare the pharmacokinetics (PK) of glepaglutide after a single
subcutaneous (SC) administration by vial/syringe and by autoinjector.
- To evaluate the safety and tolerability of glepaglutide following SC dosing
in healthy subjects.
Study design
The actual study will consist of 3 periods during each of which the subject
will stay in the research center for 5 days (4 nights) or optionally 3 days (2
nights). In each period, this will be followed by short visits to the research
center on Days 5, 6, 7, 8, and 14. Optionally, when the subject decides to stay
for 3 days (2 nights) in the clinic this will be followed by short visits on
Days 2 (evening), 3, 4, 5, 6, 7, 8, and 14. These short visits take
approximately half an hour. There will be 7 weeks in between administration of
the study compound in each period.
Day 1 is the day of administration of the study compound. In each period, 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. They will leave the research
center on Day 4 (or optionally Day 2) of each period.
Intervention
Glepaglutide will be administered as an injection under the skin (subcutaneous)
with either a syringe or an autoinjector.
There are two different treatments:
• 10 mg glepaglutide administered with a syringe
• 10 mg glepaglutide administered with an autoinjector
The subject will receive 1 treatment per period, so 3 treatments in total. The
order in which these treatments are given are shown in the table below. The
subject will be randomly assigned to sequence 1, 2 or 3:
Period 1 Period 2 Period 3
Sequence 1 Autoinjector Syringe Syringe
Sequence 2 Syringe Autoinjector Syringe
Sequence 3 Syringe Syringe Autoinjector
Study burden and risks
In a previous study, 45 healthy volunteers received a single injection of
between 1.6 mg and 96 mg glepaglutide
The most common side effect that were reported included:
• Mild injection site reactions: Reddening of the skin, especially at the
higher doses
Furthermore, doses of up to 96 mg glepaglutide did not result in significant
findings in physical, neurological, respiratory or laboratory examinations.
Glepaglutide was considered safe.
Glepaglutide is currently is being assessed in a study in patients with short
bowel syndrome, where they are dosed with glepaglutide 10mg once weekly or 10mg
twice weekly for over 2 years.
Administration of glepaglutide may trigger the production by the immune system
of antibodies directed against glepaglutide. In rare cases, these antibodies
could cross-react to GLP-2 and reduce the action of the normal production of
GLP-2 in the body. This risk is considered very small.
Administration of glepaglutide may be associated with a risk of allergic
reactions similar to those observed for other therapeutic peptides or proteins.
Subjects with known or suspected allergies to the trial products or related
products are excluded from participation in trials with glepaglutide. Mild or
moderate allergic reactions may include symptoms of rash, fever, flu-like
symptoms, nausea, headache and myalgia. Acute generalized hypersensitivity
reactions are usually very rare but may include symptoms of rash, flushing,
itching, sneezing or runny nose, abdominal pain, diarrhea, swelling of face,
tongue or throat, dizziness, lightheadedness or fainting, trouble breathing,
irregular or racing heart rate, and seizures.
Possible discomforts due to procedures
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, we will take about 340 milliliters of blood from the volunteer over
the 3 periods (21 weeks). This amount does not cause any problems in adults. To
compare: a blood donation involves 500 mL of blood being taken each time.
To make a heart tracing, electrodes will be pasted at specific locations on
your arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation.
A sample for the coronavirus test will be taken from the back of the nose and
throat using a swab. Taking the sample only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.
Sydmarken 11
Søborg DK-2860
DK
Sydmarken 11
Søborg DK-2860
DK
Listed location countries
Age
Inclusion criteria
1. Informed consent of the subject has to e obtained before any trial-related
activities are performed (trial-related activities are any procedures that
would not have been performed during normal management of the subject).
2. Subject has to be a healthy male or female aged between 18 years and 54
years, both inclusive, at screening.
3. Body mass index (BMI)of the subject has to be >20.0 kg/m2 and <29.9 kg/m2,
both inclusive, at screening.
4. Subject is willing to maintain a stable weight for the duration of the trial.
5. Subject is in overall good health according to age (medical history,
physical examination, vital signs, and laboratory assessments), as judged by
the Investigator at screening.
Exclusion criteria
1. Subject cannot have a significant medical history or clinical manifestation
of any metabolic, allergic, dermatological, hepatic, renal, hematological,
pulmonary, cardiovascular, gastrointestinal, neurological, respiratory,
endocrine, or psychiatric disorder, as determined by the Investigator.
2. Subject with a history of colon cancer or a history of other cancers within
the last 5 years.
3. The physical examination of the subject should not show clinically
significant abnormalities in the standard 12-lead ECG, or vital signs
measurements as determined by the Investigator.
4. Clinically significant abnormality in hematology, clinical chemistry, or
urinalysis as determined by the Investigator (congenital nonhemolytic
hyperbilirubinemia [eg, Gilbert*s syndrome] is acceptable).
5. Subject cannot have a history of significant hypersensitivity, intolerance,
suspected hypersensitivity to glepaglutide or related products, or allergy to
any drug compound, food, or other substance, unless approved by the
Investigator.
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 | EUCTR2019-004517-14-NL |
| CCMO | NL72557.056.20 |