A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of ONO-6414 Administered Orally in Healthy Adult Participants and Patients With Active Ulcerative Colitis

Inclusion criteria

• \<Healthy Volunteers only\>
• Male or female, age ≥18- to ≤55-year-old at the time of signing ICF.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, 12-lead ECG, vital signs measurements, and laboratory tests results, as evaluated by the investigator.
• BMI of 18.0 to 32.0 kg/m2, inclusive, and a body weight of ≥50 kg at Screening.
• \<Patients only\>
• Male or female, age ≥18-year-old at the time of signing ICF.
• A diagnosis of ulcerative colitis (UC) must have been established at least three months prior to screening.
• \<Healthy Volunteers and Patients\>
• Total abstinence, in accordance with the lifestyle of the participant, from at least 30 days prior to the first dose until at least 90 days after the last dose.
• Ability to understand the study procedures described in the ICF. Willingness and ability to comply with the protocol, and provides written informed consent prior to study participation.
• Willingness and ability to swallow study intervention tablets and/or suspension.
• Willing to take off dentures or mouth piercing at the time of dosing.

Exclusion criteria

• \<Healthy Volunteers only\>
• Mentally or legally incapacitated.
• History or presence of clinically significant medical, surgical or psychiatric condition or disease that in the opinion of the investigator or medical monitor might confound the results of the study or pose an additional risk to the participant by their participation in the study, including but not limited to a history of inflammatory bowel disease, gastritis, ulcers, gastrointestinal or rectal bleeding; history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection or history or clinical evidence of pancreatic injury or pancreatitis, history of cardiac arrhythmia (both atrial and ventricular). History of uncomplicated appendectomy and uncomplicated cholecystectomy are allowed.
• History of any major invasive surgery within 6 months before the first dosing, or minor invasive surgery within 7 days before the first dosing.
• History of hypersensitivity or idiosyncratic reaction to the study interventions, excipients (including Lactose) or related compounds, or severe food allergies.
• History of rare hereditary galactose and/or Lactose intolerance (eg, congenital lactase deficiency \[CLD\] or glucose-galactose malabsorption \[GGM\]).
• History or presence of alcoholism within 6 months before the first dosing. Alcohol abuse is defined as 7 or more drinks per week for a woman or 14 or more drinks per week for a man.
• History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
• Presence of recurring gastrointestinal symptoms (diarrhea, constipation, nausea, heartburn, etc.).
• Presence of acute gastrointestinal symptoms within 7 days before the first dosing.
• Use of medications for the timeframes and throughout the study (unless specified), with the exception of hormonal contraceptives and medications exempted by the investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study intervention or participant safety (eg, topical drug products without significant systemic absorption).
• \<Patients only\>
• Current diagnosis of indeterminate colitis, inflammatory bowel disease-unclassified, Crohn's disease, infectious colitis, or ischaemic colitis.
• Evidence of fulminant colitis or ASUC at Screening.
• The patient meets the following criteria:
• Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy for UC
• Evidence of abdominal abscess or toxic megacolon during Screening
• Imminent need for surgery or with elective surgery scheduled to occur during the study
• Positive Clostridium difficile toxin test during Screening. However, re-screening can be undertaken following successful treatment.
• Complications or history of immunologic, autoimmune or chronic inflammatory disorders (eg, uveitis, rheumatoid arthritis, ankylosing spondylitis or spondyloarthritis, psoriasis) other than UC.
• Any evidence of colonic dysplasia, adenomas or polyposis. Those that have been completely resected can be included.
• Mentally or legally incapacitated.
• A history of malignant neoplasm within the last 5 years, except for adequately treated non-metastatic basal or squamous cell cancers of the skin (within 1 year) or carcinoma in situ of the uterine cervix (within 3 years) that has been fully treated and shows no evidence of recurrence.
• History of hypersensitivity or idiosyncratic reaction to the study interventions, excipients (including Lactose) or related compounds, or severe food allergies.
• History or presence of alcoholism within 6 months before the first dosing. Alcohol abuse is defined as 7 or more drinks per week for a woman or 14 or more drinks per week for a man.
• History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
• Previously untreated UC.
• Initiation or change in the dose of the following medicines; oral sulfasalazine, aminosalicylate, oral or rectal corticosteroid, ciclosporin, mercaptopurine, azathioprine, methotrexate, anti-TNF biologic, anti-integrin, anti-IL-12/23, anti IL-23 biologics, JAK inhibitor, or S1P1 modulator.
• Fecal microbiota transplantation within 4 weeks prior to baseline endoscopy.
• Use of medications for the timeframes specified below and throughout the study (unless specified), with the exception of hormonal contraceptives and medications exempted by the investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study intervention or participant safety (eg, topical drug products without significant systemic absorption):
• depot injection or implant within 3 months prior to dosing;
• live attenuated vaccines within 1 month prior to dosing;
• MAOIs within 30 days prior to dosing and until 14 days after the last drug administration;
• any drug known to induce or inhibit hepatic drug metabolism, including St. John's Wort, within 30 days prior to dosing;
• prescription medications within 14 days prior to dosing;
• any vaccine, including COVID-19 vaccine, within 14 days prior to dosing;
• OTC medications and natural health products (including herbal remedies, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 14 days or 5 half-lives (whichever is longer) prior to dosing, with the exception of the occasional use of acetaminophen (up to 2 g daily).
• History or evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis diagnosed by a positive QFT-GIT. In case of an indeterminate, borderline, or invalid result, the QFT-GIT may be repeated once or a T-SPOT® TB test may be used to confirm the result. If the results are indeterminate/borderline at repeat testing, the participant should be excluded.
• \<Healthy Volunteers and Patients\>
• Use of any investigational drug within 30 days or 5 half-lives of that investigational drug (whichever is longer) before the first dosing.
• Abnormal clinical laboratory test results (and confirmed by a single repeat measurement, if deemed necessary) at Screening or admission.
• Positive result at Screening or admission for the urine or breath alcohol screen, or urine drug screen.
• Clinically significant abnormal laboratory test results or positive serology test results at Screening for HIV-1 Ag with HIV-1 and HIV-2 Ab, HBsAg, HBcAb (even if the result for HBcAb is positive, the negative result for HBV DNA is acceptable for study participation), or HCVAb.
• Increased CV proarrhythmic potential, confirmed with repeat per investigator discretion, at Screening or admission.
• Clinically significant abnormalities in blood pressure, pulse rate, oral temperature and respiratory rate at Screening or admission. If positive, the test should be repeated 2 more times and the average of the 3 results should be used to determine the participant's eligibility.
• Poor venous access as determined by the investigator at Screening.
• The participant smoked (including use of tobacco and/or nicotine containing products including e-cigarettes, snuff, chewing tobacco, cigars, pipes, or nicotine-replacement products) within 3 months before Screening or has a positive urine cotinine at Screening or admission, and the inability to stop using nicotine-containing products, during confinement in the study site. A smoker will be defined as any participant who reports nicotine containing products use or has a urine cotinine greater than 100 ng/mL.
• Female participant who is positive for pregnancy test or lactating or planning to become pregnant during this study or within 3 months after the last study intervention administration.
• Donation of blood ≥500 mL or significant blood loss within 56 days before the first dosing, or blood plasma or platelet donation within 14 days before the first dosing, or blood transfusion within 90 days before the first dosing.
• Participant working at or having an immediate family member (spouse or children) who works at the study site or is a staff member of the sponsor and directly involved in this trial.
• Engagement in strenuous exercise (eg, moving large bulky items, bodybuilding) within 14 days before the first dosing.
• Presence of orthodontic braces or orthodontic retention wires, or any physical findings in the mouth or tongue that would be likely to interfere with successful completion of the dosing procedure.
• Any participant who, in the opinion of the investigator, is not considered to be suitable and is unlikely to comply with the study protocol for any reason.