Study for Safety and Tolerability of TOP1288 Administered Rectally in Healthy and Ulcerative Colitis Subjects

NCT02463045 | Completed Phase 1

• 1 other identifier: TV-01
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety and tolerability of TOP1288 rectal single and multiple ascending doses in healthy subjects and multiple doses in subjects with ulcerative colitis.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (4)

• Safety as measured by adverse events

  To 7 days after the last dose

• Safety as measured by clinical laboratory tests

  To 7 days after the last dose

• Safety as measured by vital signs

  To 7 days after the last dose

• Safety as measured by ECGs

  To 7 days after the last dose

Secondary Outcomes (2)

• Pharmacokinetics profile single dose (AUC(0-24)); (Cmax); time to Cmax (tmax); apparent clearance (CL/F); apparent volume of distribution (Vz/F); mean residence time (MRT); elimination half-life (t½); elimination rate constant (λz)

  To 72 hours post dose

• Pharmacokinetics profile multiple dose AUC(0-t); (Ctrough); (Cmax,ss); (tmax,ss); (CLss/F); (Vz,ss/F); t½; λz; MRT; (0-tau) (RAUC); (RCmax);

  To 72 hours post dose

Study Arms (10)

TOP1288 1mg (or placebo)

EXPERIMENTAL

TOP1288 1mg single dose or placebo

Drug: TOP1288

TOP1288 10mg (or placebo)

EXPERIMENTAL

TOP1288 10mg single dose or placebo

Drug: TOP1288

TOP1288 100mg (or placebo)

EXPERIMENTAL

TOP1288 100mg single dose or placebo

Drug: TOP1288

TOP1288 200mg single dose or placebo

EXPERIMENTAL

TOP1288 200mg single dose or placebo

Drug: TOP1288

TOP1288 400mg dose or placebo

EXPERIMENTAL

TOP1288 400mg (200mg bid) dose or placebo

Drug: TOP1288

TOP1288 A mg or placebo

EXPERIMENTAL

TOP1288 A mg daily for 4 days

Drug: TOP1288

TOP1288 B mg or placebo

EXPERIMENTAL

TOP1288 B mg daily for 4 days

Drug: TOP1288

TOP1288 C mg or placebo

EXPERIMENTAL

TOP1288 C mg daily for 4 days

Drug: TOP1288

TOP1288 D mg or placebo

EXPERIMENTAL

TOP1288 D mg bid for 4 days

Drug: TOP1288

TOP1288 Xmg or placebo

EXPERIMENTAL

TOP1288 X mg od or bid for 4 days

Drug: TOP1288

Interventions

TOP1288 DRUG

Also known as: TOP1288 Placebo

TOP1288 100mg (or placebo); TOP1288 10mg (or placebo); TOP1288 1mg (or placebo); TOP1288 200mg single dose or placebo; TOP1288 400mg dose or placebo; TOP1288 A mg or placebo; TOP1288 B mg or placebo; TOP1288 C mg or placebo; TOP1288 D mg or placebo; TOP1288 Xmg or placebo

Eligibility Criteria

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

You may qualify if:

• Healthy Subjects and Ulcerative Colitis Subjects
• Male or Female aged between 18 and 55 years (inclusive)
• Female subjects negative serum pregnancy test at Screening, non child-bearing potential.
• Body Mass Index between 18.0 and 29.9 kg/m2
• Good physical and mental health (other than ulcerative colitis for subjects in Part 3)
• Clinical laboratory test results within the reference ranges of the testing laboratory (with the exception of ulcerative colitis subjects with laboratory abnormalities consistent with their disease activity which will be allowed at Investigator's and the Sponsor's study physician/medical monitor's discretion)
• Blood pressure and pulse within normal range
• Specific to Ulcerative Colitis Subjects
• Documented diagnosis of ulcerative colitis of at least 6 months duration confirmed by sigmoidoscopy
• Documented disease extending at least 15cm proximal from the anal verge
• Subject has experienced symptoms of ulcerative colitis on oral 5-ASA therapy in the 14 days before Screening and has been on stable dose regimen (no more than 2.4g/day) for at least 4 weeks duration prior to Day 1 and is willing to continue on this regimen for the duration of the study

You may not qualify if:

• Healthy Subjects and Ulcerative Colitis Subjects
• Participation in another study of investigational medication within the last 3 months or 5 half-lives of the investigational medication, whichever is longer
• Positive for HIV 1/2 antibodies, hepatitis B surface antigen or hepatitis C antibodies
• Any prescription or non-prescription medications within prior 14 days (other than ulcerative colitis for subjects in Part 3 for whom a stable dose regimen of oral 5-ASA (no more than 2.4g/day) for at least 4 weeks before Day 1 is allowed and required)
• Consumption of any products containing caffeine or xanthine-related substances, foods or beverages containing Seville-type oranges or poppy seeds within 72 hours prior to admission
• Any acute or chronic illness (other than ulcerative colitis in Part 3) 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 Investigator and the Sponsor's study physician/medical monitor would interfere with the subject's participation in the study
• Cardiovascular or cerebrovascular disease, including hypertension, angina, ischemic heart disease, transient ischaemic attacks, stroke and peripheral arterial disease sufficient to cause symptoms and/or require therapy to maintain stable status
• Abnormalities in haematology or ECG.
• Renal or liver impairment
• Active neoplastic disease or history of neoplastic disease within 5 years before Screening
• Specific to Ulcerative Colitis Subjects
• Documented history of ulcerative colitis in immediate need of dose escalation of maintenance 5-aminosalicylate therapy.
• Proctitis at baseline endoscopy (on Day 1).
• Started oral 5-aminosalicylate within 4 weeks prior to baseline endoscopy or is not yet on a stable dose.
• Any medication administered per rectum within 1 week prior to baseline endoscopy.

Sponsors & Collaborators

• Topivert Pharma Ltd: lead

Study Sites (1)

CTU

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2015
• First Posted: June 4, 2015
• Study Start: May 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 23, 2017

Record last verified: 2016-09

Locations

GB (1)