Ulcerative ColitisPhase 1NCT02463045
Study for Safety and Tolerability of TOP1288 Administered Rectally in Healthy and Ulcerative Colitis Subjects
A Phase 1 study testing TOP1288 in people with Ulcerative Colitis, run by Topivert Pharma Ltd at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- TOP1288
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2015to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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.
- Oral or parenteral steroid within 2 weeks before the baseline endoscopy.
- Systemic immunomodulatory therapy (with the exception of azathioprine or 6-mercaptopurine in a dose regimen that is deemed acceptable for participation in the judgement of the Principal Investigator) within 12 weeks prior to baseline endoscopy.
- Previous treatment with biologic agents (including anti-TNF agents and vedolizumab) prior to baseline endoscopy.
- Mayo Score Physician's global assessment of 3, i.e., severe disease.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study to Evaluate the Safety/Tolerability and Pharmacokinetics of TOP1288 Rectal Single and Multiple Ascending Doses in Healthy Subjects and Multiple Doses in Subjects With Ulcerative Colitis
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.
Read the detailed description
TOP1288, a narrow spectrum protein kinase inhibitor, is being developed as a novel, non-absorbed treatment for ulcerative colitis (UC). UC is a disease of unknown cause characterised by inflammation of the lining of the large intestine and manifesting with abdominal pain and bloody diarrhoea. TOP1288 given rectally has a local anti-inflammatory action in experimental models of UC. The present study will be the first time TOP1288 has been given to humans and explores the safety, tolerability and how the body handles (absorbs, distributes and eliminates) TOP1288 and seeks evidence of the biochemical effect of the drug in the body. The study is in three parts: Part 1 investigates single doses in groups of healthy volunteers, each group dosed with an increased dose provided the drug was safe and well tolerated at the previous level. Part 2 investigates multiple ascending doses in healthy volunteers each group dosed with an increased dose provided the drug was safe and well tolerated at the previous level. Part 3 investigates one dose level by administering that dose in patient volunteers with UC. The study design is adaptive - that is after the first dose level in Part 1, which is predefined, the exact dose and dose-intervals can be modified from a pre-set plan by a Safety Review Committee in the light of the emerging results.
- Conditions
- Ulcerative Colitis
- Being tested
- TOP1288
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TOP1288Drug
Also called TOP1288 Placebo
| Study group | Role | What they receive |
|---|---|---|
| TOP1288 1mg (or placebo) | Experimental | TOP1288 1mg single dose or placebo Receives: Drug: TOP1288 |
| TOP1288 10mg (or placebo) | Experimental | TOP1288 10mg single dose or placebo Receives: Drug: TOP1288 |
| TOP1288 100mg (or placebo) | Experimental | TOP1288 100mg single dose or placebo Receives: Drug: TOP1288 |
| TOP1288 200mg single dose or placebo | Experimental | TOP1288 200mg single dose or placebo Receives: Drug: TOP1288 |
| TOP1288 400mg dose or placebo | Experimental | TOP1288 400mg (200mg bid) dose or placebo Receives: Drug: TOP1288 |
| TOP1288 A mg or placebo | Experimental | TOP1288 A mg daily for 4 days Receives: Drug: TOP1288 |
| TOP1288 B mg or placebo | Experimental | TOP1288 B mg daily for 4 days Receives: Drug: TOP1288 |
| TOP1288 C mg or placebo | Experimental | TOP1288 C mg daily for 4 days Receives: Drug: TOP1288 |
| TOP1288 D mg or placebo | Experimental | TOP1288 D mg bid for 4 days Receives: Drug: TOP1288 |
| TOP1288 Xmg or placebo | Experimental | TOP1288 X mg od or bid for 4 days Receives: Drug: TOP1288 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as measured by adverse events
Measured: To 7 days after the last dose
Safety as measured by clinical laboratory tests
Measured: To 7 days after the last dose
Safety as measured by vital signs
Measured: To 7 days after the last dose
Safety as measured by ECGs
Measured: 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)
Single-dose PK (Day 1 Part 1, Part 2 and Part 3): Area under the concentration-time curve (AUC) from zero extrapolated to infinity (AUC(0-inf)); AUC from zero to the time of the last quantifiable concentration (AUC(0-t)); AUC from zero to the time of 12 hours (AUC(0-12)); AUC from zero to the time of 24 hours (AUC(0-24)); observed maximum concentration (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).
Measured: 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);
Multiple-dose PK (Day 4 in Part 2 and Part 3): AUC(0-t); AUC during the dosing interval (AUC(0-tau)); predose concentration (Ctrough); observed maximum concentration after multiple dosing (Cmax,ss); time to Cmax,ss (tmax,ss); apparent clearance at steady state (CLss/F); apparent volume of distribution at steady state (Vz,ss/F); t½; λz; MRT; accumulation ratio for AUC(0-tau) (RAUC); accumulation ratio for Cmax (RCmax); time independency factor.
Measured: To 72 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startMay 2015
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Topivert Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02463045
- Sponsor's protocol ID
- TV-01
- Status last verified
- Sep 2016
- First submitted
- 26 May 2015
- Last updated
- 23 May 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Evaluate the Safety/Tolerability and Pharmacokinetics of TOP1288 Rectal Single and Multiple Ascending Doses in Healthy Subjects and Multiple Doses in Subjects With Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT02463045
- Acronym / sponsor ID
- TV-01
- Conditions
- Ulcerative Colitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Topivert Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- May 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 4 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
TOP1288, a narrow spectrum protein kinase inhibitor, is being developed as a novel, non-absorbed treatment for ulcerative colitis (UC). UC is a disease of unknown cause characterised by inflammation of the lining of the large intestine and manifesting with abdominal pain and bloody diarrhoea. TOP1288 given rectally has a local anti-inflammatory action in experimental models of UC. The present study will be the first time TOP1288 has been given to humans and explores the safety, tolerability and how the body handles (absorbs, distributes and eliminates) TOP1288 and seeks evidence of the biochemical effect of the drug in the body. The study is in three parts: Part 1 investigates single doses in groups of healthy volunteers, each group dosed with an increased dose provided the drug was safe and well tolerated at the previous level. Part 2 investigates multiple ascending doses in healthy volunteers each group dosed with an increased dose provided the drug was safe and well tolerated at the previous level. Part 3 investigates one dose level by administering that dose in patient volunteers with UC. The study design is adaptive - that is after the first dose level in Part 1, which is predefined, the exact dose and dose-intervals can be modified from a pre-set plan by a Safety Review Committee in the light of the emerging results.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| TOP1288 1mg (or placebo) | Experimental | Drug: TOP1288TOP1288 1mg single dose or placebo |
| TOP1288 10mg (or placebo) | Experimental | Drug: TOP1288TOP1288 10mg single dose or placebo |
| TOP1288 100mg (or placebo) | Experimental | Drug: TOP1288TOP1288 100mg single dose or placebo |
| TOP1288 200mg single dose or placebo | Experimental | Drug: TOP1288TOP1288 200mg single dose or placebo |
| TOP1288 400mg dose or placebo | Experimental | Drug: TOP1288TOP1288 400mg (200mg bid) dose or placebo |
| TOP1288 A mg or placebo | Experimental | Drug: TOP1288TOP1288 A mg daily for 4 days |
| TOP1288 B mg or placebo | Experimental | Drug: TOP1288TOP1288 B mg daily for 4 days |
| TOP1288 C mg or placebo | Experimental | Drug: TOP1288TOP1288 C mg daily for 4 days |
| TOP1288 D mg or placebo | Experimental | Drug: TOP1288TOP1288 D mg bid for 4 days |
| TOP1288 Xmg or placebo | Experimental | Drug: TOP1288TOP1288 X mg od or bid for 4 days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TOP1288Also: TOP1288 Placebo | Drug | 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 |
Primary outcome
Safety as measured by adverse events
Time frame: To 7 days after the last dose
Safety as measured by clinical laboratory tests
Time frame: To 7 days after the last dose
Safety as measured by vital signs
Time frame: To 7 days after the last dose
Safety as measured by ECGs
Time frame: To 7 days after the last dose
2 secondary outcomes
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)
Time frame: 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);
Time frame: To 72 hours post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TOP1288 in people with Ulcerative Colitis, run by Topivert Pharma Ltd at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as measured by adverse events (time frame: To 7 days after the last dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2017.