E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum. People with UC suffer from urgent passage of bloody stools, often with abdominal or pelvic cramping. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the pharmacokinetics (PK) of 5-aminosalycylic acid (5-ASA) and its major metabolite acetyl 5-aminosalycylic acid (Ac-5-ASA) after administration of MMX mesalamine at 3 different doses (30mg/kg/day, 60mg/kg/day, or 100mg/kg/day) for 7 days in children and adolescents with a history of ulcerative colitis. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of MMX mesalamine at 3 different doses (30mg/kg/day, 60mg/kg/day, or 100mg/kg/day) after administration for 7 days in children and adolescents with a history of ulcerative colitis.
- To evaluate the extent of absorption of 5-ASA from MMX mesalamine at steady-state, as defined by the total urinary excretion of 5-ASA and Ac-5-ASA, expressed as a percentage of the administered dose.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject’s parent or legally acceptable representative (LAR) must provide signature of informed consent and there must be documentation of assent by the subject indicating the subject is aware of the investigational nature of the study, able and willing to participate in the study, and aware of the required restrictions and procedures
2. Males and females aged 5-17 years at the time of the first dose of investigational medicinal product
3. Subject has a documented history of ulcerative colitis for at least 3 months prior to first dose of investigational medicinal product, as confirmed by medical records, a physician referral, similar documentation, or investigator assessment of date of diagnosis, clinical course, history of flares, and prior medications as reported by the subject/parent/LAR
4. Subjects who are currently on a 5-ASA or product(s) containing or metabolized to mesalamine must have been on a stable regimen for at least 4 weeks prior to first dose of investigational medicinal product. The subject must be willing and the investigator deem it medically acceptable, to replace the current therapy with the investigational medicinal product for the 8-day study treatment period
5. Subjects who are not currently on a drug regimen, or on a 5-ASA or product containing or metabolized to mesalamine, must have been on a stable regimen for at least 4 weeks prior to first dose of investigational medicinal product
6. Good general health (except for ulcerative colitis and associated sequelae) based on medical history, vital signs, electrocardiogram (ECG), physical examination, and clinical laboratory results at Screening (Days –28 to –2)
7. Body weight of 18kg-82kg inclusive, at Screening (Days –28 to –2) and Baseline (Day –1)
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E.4 | Principal exclusion criteria |
1. Current or recurrent disease (e.g., cardiovascular, renal, liver, malignancy or other conditions) that could affect the colon, the action, absorption or disposition of the investigational medicinal product, or clinical or laboratory assessments with the exception of their existing ulcerative colitis
2. Ulcerative Colitis known to be confined to the rectum (isolated rectal proctitis)
3. Any history of hepatic impairment as confirmed by medical history
4. History of moderate to severe renal impairment defined as glomerular filtration rate <60ml/min/1.73m2 as confirmed by medical history (based on the Schwartz equation: CrCl (ml/min/1.73m2)= [length (cm) x k] / Scr)
5. A history of allergy, hypersensitivity, or poor tolerability to salicylates or aminosalicylates (5-ASA)
6. Any history of Reyes syndrome
7. Any history of pancreatitis
8. The use of systemic or rectal steroids within the last 4 weeks, immunomodulators within the last 6 weeks, biologics within 6 months, antibiotic use within the last 7 days prior to the first dose of investigational medicinal product
9. Repeated use of any anti-inflammatory drugs (including nonsteroidal anti-inflammatory drugs but excluding 5-ASA or products containing or metabolized to mesalamine [oral or rectal]) within 7 days prior to the first dose of investigational medicinal product
10. If anti-diarrheals and/or antispasmodics are being used, subjects need to be on a stable dose regimen for 3 days prior to the first dose of investigational medicinal product
11. Use of another investigational medicinal product within 30 days prior to receiving the first dose of investigational medicinal product or active enrollment in another drug or vaccine clinical trial; concurrent participation in an observational (i.e. Registry) study would not be exclusionary, as long as all other inclusion and exclusion criteria are met
12. Current or relevant history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder (including subjects underlying ulcerative colitis .e.g., concurrent severe flare) that may require new treatment or changes to their current treatment regimen or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational medicinal product or procedures
13. Subjects with asthma are excluded only if they are known to be 5-ASA-sensitive
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints of maximum plasma concentration at steady-state (Cmaxss) and area under the plasma concentration within a dosing interval at steady-state (AUCss) for 5-ASA and Ac-5-ASA will be assessed to determine the extent of systemic exposure to MMX Mesalamine. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study Days 5, 6, 7, and 8 |
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E.5.2 | Secondary end point(s) |
The secondary endpoint of safety and tolerability will include an assessment of adverse events, clinical laboratory results, vitals signs, and other collected clinical parameters. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening visit through the Follow-up contact |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No compator drug or placebo is being used |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 28 |
E.8.9.2 | In all countries concerned by the trial days | 0 |