Primary:1. To characterize the safety and tolerability of multiple oral doses of K-196 alone and in combination with naproxen/omeprazole in healthy subjects.Secondary:1. To assess the effects of K-196 compared to placebo on the proportion of…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To characterize the safety and tolerability of multiple oral doses of K-196
alone and in combination with naproxen/omeprazole in healthy subjects.
Secondary outcome
Small bowel mucosal breaks; PK
Background summary
Treatment of Crohn*s disease (CD) and ulcerative colitis (UC) is based on the
disease severity and aimed at alleviating symptoms, improving quality of life,
and inducing disease remission. Currently available treatments target the
intestinal inflammation associated with disease, typically with general
anti-inflammatory medications, including corticosteroids and aminosalicylates,
followed by immunomodulatory therapies. Despite significant treatment
options, IBD remains an area of critical unmet need with less than 50% of
patients with moderate-severe disease attaining long-term clinical remission.
In vitro, K-196 was shown to protect against low calcium-induced disassembly of
intercellular junctions resulting in reduced permeability of test probes across
cellular monolayers. In a dextransodium sulfate (DSS) chemical injury colitis
model, K-196 prevented DSS-induced intestinal permeability, body weight loss,
rectal bleeding, and diarrhea. K-196 treatment reduced levels of fecal
lipocalin, an abundant neutrophil protein shed into stool that is used as a
marker of inflammation and barrier integrity. In a DSS recovery paradigm where
K-196 dosing was initiated only after the onset of colitis, K-196 treatment
resulted in less body weight loss, bleeding, and diarrhea vs. vehicle.
Additionally, in a 5-fluoruracil-induced injury model, K-196 prevented the
development of diarrhea, reduced body weight loss, and reduced fecal lipocalin
levels. Altogether these data suggest that K-196 can modulate barrier function
by altering permeability of intercellular junctions and by protecting the
viability of epithelial cells against cytotoxic stressors.
Study objective
Primary:
1. To characterize the safety and tolerability of multiple oral doses of K-196
alone and in combination with naproxen/omeprazole in healthy subjects.
Secondary:
1. To assess the effects of K-196 compared to placebo on the proportion of
subjects with 1 or more small bowel mucosal breaks detected by video capsule
endoscopy (VCE) following naproxen/omeprazole.
2. To assess the effects of K-196 compared to placebo on the mean number of
small bowel mucosal breaks detected by VCE following naproxen/omeprazole.
3. To characterize the pharmacokinetics on K-196 on Day 14 in healthy subjects
(AUC0-8h, Cmax, Ctrough).
Study design
This is a 14-day, randomized, double blind (Sponsor open), placebo-controlled,
parallel-group trial.
K-196 or placebo will be administered in a double-blind manner.
Naproxen/omeprazole will be open-label.
Intervention
K-196 capsules or matching placebo, naproxen, omeprazole.
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the overall benefitrisk in the CSP
for further information.
East 29th Street 430
New York NY 10016
US
East 29th Street 430
New York NY 10016
US
Listed location countries
Age
Inclusion criteria
1. Understand the trial procedures and agree to participate by providing
written informed consent.
2. Be willing and able to comply with all trial procedures and restrictions.
3. Be healthy between 18 to 59 years of age, inclusive, at the Screening Visit.
4. Have a Body Mass Index (BMI) >=18.0 and <30.0 (kg/m2) at the Screening Visit.
5. Be a nonsmoker who has not used tobacco or nicotine-containing products
(e.g., nicotine patch) for at least 3 months before administration of the
initial dose of trial drug and agrees to abstain from smoking tobacco or the
use of nicotine-containing products while on study.
6. Be judged to be in good health by the Investigator, based on clinical
evaluations including laboratory safety tests, medical history, physical
examination, 12-lead ECG, and vital sign measurements performed at the
Screening Visit and before administration of the initial dose of trial drug.
Exclusion criteria
1. Has participated in another investigational study within the following time
period: 30 days, 5 half-lives or twice the duration of the biological effect of
the investigational product (whichever is longer or based on local regulations)
prior to the Screening Visit. The window will be derived from the date of the
last study procedure and/or AE related to the study procedure in the previous
study to the Screening Visit of the current study.
2. Is an employee or immediate family member (e.g., spouse, parent, child,
sibling) of the Sponsor or study site.
3. Has a history of significant multiple and/or severe allergies (e.g., food,
drug, latex allergy) or has had an anaphylactic reaction or significant
intolerance to prescription or nonprescription drugs or food.
4. Has a known hypersensitivity or contraindication to any component of K-196,
related compounds or its excipients.
5. Has known hypersensitivity to naproxen or any components of the drug product
6. Has history of asthma, urticaria or other allergic-type reactions after
taking naproxen or other NSAIDs.
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 | EUCTR2022-003522-42-NL |
| CCMO | NL83065.056.22 |