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A Study of PALI-2108 in Healthy Volunteers, Patients With Ulcerative Colitis, and Patients With Fibrostenosing Crohn's Disease
Bu çalışma, PALI-2108 adlı ilacı sağlıklı gönüllülerde, ülseratif kolit (ulcerative colitis) hastalarında ve daralma yapan (fibrostenozan) Crohn hastalığı (Crohn's disease) olan hastalarda incelemektedir. Çalışmaya, 18-60 yaş arası sağlıklı yetişkinler ile ilgili bağırsak hastalığı tanısı bulunan hastalar katılabilmektedir. Çalışma Faz 1 aşamasında yürütülmektedir; şu an katılımcı almamakta ancak devam etmektedir (active, not recruiting).
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria
1. Provision of signed and dated informed consent form (ICF)
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Aged at least 18 years but not older than 60 years
4. Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
5. Non- or ex-smoker
6. Healthy adult male or female
7. Have no clinically significant (CS) diseases captured in the medical history or evidence of CS findings on the physical examination (including vital signs) and/or ECG, as determined by an Investigator
8. Provision of signed and dated ICF
9. Stated willingness to comply with all study procedures and availability for the duration of the study
10. If male, meets one of the following criteria:
1. Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last study drug administration. An acceptable method of contraception includes one of the following:
* Abstinence from heterosexual intercourse
* Male condom with spermicide or male condom with a vaginal spermicide Or
2. Is unable to procreate; defined as surgically sterile
If female, meets one of the following criteria:
1. Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:
* Abstinence from heterosexual intercourse from 14 days prior to the Screening visit through to at least 30 days after the last dose of the study drug
* Use of 1 highly effective method in combination with 1 effective method of contraception.
• The following are examples of highly effective contraceptive methods, used from at least 28 days prior to the Screening visit through to at least 30 days after the last dose of the study drug:
* Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, or transdermal patch)
* Intrauterine device
* Male partner vasectomized at least 6 months prior to the Screening visit
• The following are examples of effective contraceptive methods, used from the Screening visit through to at least 30 days after the last dose of the study drug:
* Male condom with spermicide
* Female condom, or cervical cap, or diaphragm, each used with spermicide
* Contraceptive sponge
2. Is of non-childbearing potential, defined as surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or is in a postmenopausal state (ie, at least 1 year without messes and without an alternative medical condition prior to the Screening visit)
11. Diagnosis of ileal or ileocolonic CD based on supporting guideline criteria established at least 3 months prior to Screening, i.e.:
c) Clinically symptomatic fibrostenosing Crohn's disease, defined by ≥1 obstructive symptom attributable to the index ileal stricture within the prior 12 weeks and corroborated at Screening by the Stricturing Crohn's Disease patient-reported questionnaire (SPRO).
d) Symptoms must be accompanied by an ileal stricture within reach of the endoscope.
12. Screening IUS confirms the presence of at least 1 stricture in the terminal ileum or proximal colon, within reach of an endoscope (passable or non-passable). Strictures should be noncritical, naïve or anastomotic stricture(s), caused by CD and confirmed by endoscopy.
13. Stable background therapy for CD and agree to maintain background therapy for the study duration.
14. Patients may or may not experience stricture related symptoms, such as abdominal pain, during Screening
15. Willingness to follow a stable diet during the study
Exclusion Criteria
1. Female who is lactating
2. Female who is pregnant according to the pregnancy test at Screening or Day -1
3. History of significant hypersensitivity to PALI-2108 or any other PDE-4 inhibitor (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
4. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability or transit
5. Presence of history of renal disease
6. History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
7. An active infection or a recent history of serious infections 30 days prior to first study drug administration
8. Presence of CS vital sign and/or ECG abnormalities (based on the average of triplicate ECG readings) at the Screening visit, as defined by medical judgment
9. Major surgery in the 4 weeks prior to the first study drug administration
10. Vaccination with any live vaccine within 4 weeks prior to study drug administration
11. Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
12. Any CS illness in the 28 days prior to the first study drug administration
13. Use of St. John's wort in the 28 days prior to the first study drug administration
14. Any history of tuberculosis
15. Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration
16. Positive Screening results to HIV antigen/antibody (Ag/Ab) combo, hepatitis B surface antigen, or hepatitis C virus tests
17. Any other CS abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
18. Inclusion in a previous group for this clinical study
19. Intake of PALI-2108 in the 28 days prior to the first study drug administration
20. Intake of an investigational drug in the 28 days prior to the first study drug administration
21. Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
22. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration
23. History or current diagnosis of UC, indeterminate colitis, ischemic colitis, nonsteroidal anti-inflammatory drug-induced colitis, idiopathic colitis (ie, colitis not consistent with CD), radiation colitis, microscopic colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
24. CD related complications (previous extensive small bowel resection, ileorectal anastomosis, proctocolectomy, short bowel syndrome, ileostomy \[diverting or end\], colostomy, small bowel stoma, ileoanal pouch, inactive fistulae in or adjacent to an ileal stricture, anal and perianal stricture, active intra-abdominal or perianal abscess that has not been appropriately treated, abscess in relation to the stricture, toxic megacolon, very severe inflammation, or presence of deep ulceration in the colon or terminal ileum).
25. Ileitis not associated with CD (e.g., ileitis associated with infections, spondyloarthropathies, ischemia, etc.).
26. Strictures that cannot be reached by ileocolonoscopy
27. Severe FSCD based on symptoms, or unstable disease
28. Expected to require hospitalization, endoscopic balloon dilation, surgical resection, or additional therapy during the study
29. Receiving cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks of screening or Janus kinase inhibitor therapy within 4 weeks of screening.
30. Current or history of vasculitis, valvulopathy or large vessel disorder or major abnormalities documented by cardiac echocardiography with Doppler