Study for Safety and Tolerability of TOP1288 Administered Orally in Healthy Subjects

NCT03071081 | Completed Phase 1 DMC

• 1 other identifier: TOP1288-TV-03
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety and tolerability of TOP1288 oral single ascending and multiple doses in healthy subjects.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (4)

• Safety (AEs)

  As measured by adverse events

  To 7 days after last dose

• Safety (ECGs)

  As measured by ECGs

  To 7 days after last dose

• Safety (vital signs)

  As measured by vital signs

  To 7 days after last dose

• Safety (clinical lab tests)

  As measured by clinical laboratory tests

  To 7 days after last dose

Secondary Outcomes (11)

• Pharmacokinetic profile Cmax

  0-48 hours

• Pharmacokinetic profile AUC

  0-48 hours

• Pharmacokinetic profile AUC0-12h

  0-12 hours

• Pharmacokinetic profile AUC0-24h

  0-24 hours

• Pharmacokinetic profile AUC0-t

  0-48 hours

Study Arms (6)

TOP1288 200mg BID

EXPERIMENTAL

1 day dosing

Drug: TOP1288

Placebo to TOP1288 200mg BID

PLACEBO COMPARATOR

1 day dosing

Drug: Placebo to TOP1288

TOP1288 1g BID

EXPERIMENTAL

1 day dosing

Drug: TOP1288

Placebo to TOP1288 1g BID

PLACEBO COMPARATOR

1 day dosing

Drug: Placebo to TOP1288

TOP1288 Xg (where X is <=1g) BID

EXPERIMENTAL

7 days dosing

Drug: TOP1288

Placebo to TOP1288 Xg

PLACEBO COMPARATOR

7 days dosing

Drug: Placebo to TOP1288

Interventions

TOP1288 DRUG

Oral TOP1288

TOP1288 1g BID; TOP1288 200mg BID; TOP1288 Xg (where X is <=1g) BID

Placebo to TOP1288 DRUG

Oral placebo to TOP1288

Placebo to TOP1288 1g BID; Placebo to TOP1288 200mg BID; Placebo to TOP1288 Xg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a healthy male, aged between 18 and 55 years of age (inclusive) at Screening.
• Subject has a body mass index (BMI) of between 18.0 and 29.9 kg/m2 (inclusive), with a body weight of at least 50 kg at Screening.
• Subject is in good physical and mental health in the opinion of the Investigator.
• Subject has clinical laboratory test results within the reference ranges of the testing laboratory unless results outside the reference ranges are deemed not clinically significant by the Investigator at Screening and Day -1.
• Subject has a supine blood pressure and pulse rate within the normal range after 5 minutes' rest (systolic blood pressure: 90 to 140 mmHg, diastolic blood pressure: 40 to 90 mmHg, pulse rate: 40 to 90 beats per minute) at Screening and Day -1.
• Subjects must be willing to comply with the contraception restrictions of the protocol for this study.
• Subject has regular bowel opening of usually 1 motion per day of normal consistency.

You may not qualify if:

• Subject has participated in another study of an investigational medication (or a medical device) within the last 3 months or 5 half-lives of the investigational medication, whichever is longer, prior to the first day or dosing.
• Subject has made a blood donation (\> 400 mL) or had a comparable blood loss (\> 350 mL) within the last 3 months prior to first administration of study drug.
• Subject tests positive for human immunodeficiency virus (HIV)-1/2 antibodies, hepatitis B surface antigen, or hepatitis C antibodies at Screening.
• Subject has a history of alcohol and/or drug abuse.
• Subject has an alcohol consumption of more than 21 units of alcohol per week.
• Subject tests positive for alcohol and/or drugs (urine tests) at Screening or admission.
• Subject has received any prescription or non-prescription medications, including over-the-counter medications, nutraceuticals (e.g., St. John's Wort, ginseng, kava kava, Ginkgo biloba and melatonin), foods or beverages containing grapefruit and vitamin supplements within 14 days prior to admission (Day -1) or nutraceuticals containing caffeine- or xanthine-related substances within 72 hours prior to admission (Day -1). Foods or beverages containing Seville-type (sour) oranges, or poppy seeds are also excluded within this time period.
• The subject has a history of daily consumption of 5 or more cups of coffee or tea.
• Subject has a known hypersensitivity to any components of the study drug.
• Subject has any history of any clinically significant acute or chronic condition affecting the colon and/or rectum and/or anus, including haemorrhoids and irritable bowel syndrome, sufficient to cause symptoms and/or that in the judgement of the PI and the Sponsor's study Physician/Medical Monitor would interfere with the subject's participation in the study.
• Any findings on pre-dose endoscopy that in the PI's judgement would interfere with subject participation in the study.
• Subject has acute or chronic condition affecting GI motility such as constipation or diarrhoea that would, in the judgement of the PI and the Sponsor's study Physician/Medical Monitor, interfere with the subject's participation in the study
• Subject has cardiovascular or cerebrovascular disease, including hypertension, angina, ischaemic heart disease, transient ischaemic attacks, stroke and peripheral arterial disease sufficient to cause symptoms and/or require therapy to maintain stable status.
• Subject has an active infection (e.g., sepsis, pneumonia, abscess) or has had a serious infection (resulting in hospitalisation or requiring parenteral antibiotic treatment) within 6 weeks prior to study drug administration.
• Subject has a history of positive tuberculosis test or evidence of possible tuberculosis or latent tuberculosis infection at Screening (interferon gamma release assay testing) that cannot be attributed to a prior Bacillus Calmette-Guérin inoculation.

Sponsors & Collaborators

• Topivert Pharma Ltd: lead

Study Sites (1)

PAREXEL Early Phase Clinical Unit

London, United Kingdom

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Muna Albayaty, MBChB, FFPM

  Copenhagen Trial Unit, Center for Clinical Intervention Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3 dose groups (2 arms per dose group)

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: March 6, 2017
• Study Start: February 8, 2017
• Primary Completion: June 2, 2017
• Study Completion: June 2, 2017
• Last Updated: September 20, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)