Safety and Pharmacokinetics of MMX Mesalamine in Children and Adolescents With Ulcerative Colitis

A Phase 1, Multicenter, Open-label Study to Determine the Safety and Pharmacokinetics of MMX Mesalamine Following Administration in Children and Adolescents With Ulcerative Colitis

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01130844

Enrollment

Registered

2010-05-26

Start date

2010-10-08

Completion date

2013-06-27

Last updated

2021-06-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ulcerative Colitis

Brief summary

The purpose of this study is to determine the safety and pharmacokinetics of MMX mesalamine following administration in children and adolescents with ulcerative colitis.

Interventions

DRUGMMX Mesalamine

30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

5 Years to 17 Years

Healthy volunteers

Inclusion criteria

1. Subjects aged 5-17 years, with appropriately obtained informed consent and assent. 2. Subject has a documented history of ulcerative colitis for at least 3 months. 3. Subjects who are currently on 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. 4. 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 at least 4 weeks prior first dose of investigational medicinal product. 5. Body weight of 18kg-82kg inclusive.

Exclusion criteria

1. Current or recurrent disease (eg cardiovascular, renal, liver, malignancy or other conditions) that could affect the colon, the action, absorption or disposition of the IMP, 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 or moderate to severe renal impairment. 4. 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.

Design outcomes

Primary

Measure	Time frame	Description
CL of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State	Over a 24-hour period starting on day 7	—
AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State	2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7	—
Cmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State	Over a 24-hour period starting on day 7	—
Tmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State	Over a 24-hour period starting on day 7	—
Area Under the Plasma Concentration Versus Time Curve (AUC) of MMX Mesalamine (5-ASA) at Steady State	2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Maximum Plasma Concentration (Cmax) of MMX Mesalamine (5-ASA) at Steady State	Over a 24-hour period starting on day 7	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.
Time to Maximum Plasma Concentration (Tmax) of MMX Mesalamine (5-ASA) at Steady State	Over a 24-hour period starting on day 7	Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.
Total Body Clearance (CL) of MMX Mesalamine (5-ASA) at Steady State	Over a 24-hour period starting on day 7	Clearance of a substance from the blood by the kidneys.

Secondary

Measure	Time frame	Description
Cumulative Amount of MMX Mesalamine (5-ASA) Recovered in Urine at Steady State	Over a 24-hour period starting on day 7	—
Cumulative Amount of MMX Mesalamine Major Metabolite (Ac-5-ASA) Recovered in Urine at Steady State	Over a 24-hour period starting on day 7	—
Percentage of Dose Absorbed For MMX Mesalamine (5-ASA) in Urine at Steady State	Over a 24-hour period starting on day 7	The percentage of the dose absorbed was calculated as: 100 x (Xu0-24h 5-ASA + \[0.7847\* Xu0-24h Ac-5-ASA\])/dose, where 0.7847 is the ratio of the molecular weight of 5-ASA (153.14) to the molecular weight of Ac-5-ASA (195.15). Xu0-24h is equal to the cumulative amount recovered in urine in the time interval of 0 to 24 hours.

Countries

Australia, Poland, Slovakia, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
MMX Mesalamine (30mg/kg) MMX Mesalamine: 30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.	21
MMX Mesalamine (60 mg/kg) MMX Mesalamine: 60 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.	22
MMX Mesalamine (100 mg/kg) MMX Mesalamine: 100 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.	9
Total	52

Baseline characteristics

Characteristic	MMX Mesalamine (30mg/kg)	MMX Mesalamine (60 mg/kg)	MMX Mesalamine (100 mg/kg)	Total
Age, Continuous	14.0 years STANDARD_DEVIATION 2.88	13.9 years STANDARD_DEVIATION 2.59	10.6 years STANDARD_DEVIATION 3.28	13.3 years STANDARD_DEVIATION 3.06
Age, Customized 5 to 17 years, inclusive	21 Participants	22 Participants	9 Participants	52 Participants
Region of Enrollment Poland	16 Participants	17 Participants	8 Participants	41 Participants
Region of Enrollment Slovakia	2 Participants	1 Participants	0 Participants	3 Participants
Region of Enrollment United States	3 Participants	4 Participants	1 Participants	8 Participants
Sex: Female, Male Female	14 Participants	11 Participants	5 Participants	30 Participants
Sex: Female, Male Male	7 Participants	11 Participants	4 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 21	0 / 22	0 / 9
serious Total, serious adverse events	0 / 21	0 / 22	0 / 9

Outcome results

Primary

Area Under the Plasma Concentration Versus Time Curve (AUC) of MMX Mesalamine (5-ASA) at Steady State

AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

Time frame: 2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7

Population: The Pharmacokinetic Set (PKS) consisted of all subjects in the Safety Analysis Set who generated sufficient plasma samples to allow reliable determination of Cmax and AUC. The Safety Analysis Set consisted of subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm	Measure	Value (MEAN)	Dispersion
MMX Mesalamine (30mg/kg)	Area Under the Plasma Concentration Versus Time Curve (AUC) of MMX Mesalamine (5-ASA) at Steady State	21411 ug*h/L	Standard Deviation 11081
MMX Mesalamine (60 mg/kg)	Area Under the Plasma Concentration Versus Time Curve (AUC) of MMX Mesalamine (5-ASA) at Steady State	46173 ug*h/L	Standard Deviation 22864
MMX Mesalamine (100 mg/kg)	Area Under the Plasma Concentration Versus Time Curve (AUC) of MMX Mesalamine (5-ASA) at Steady State	49213 ug*h/L	Standard Deviation 17664

Primary

AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State

Time frame: 2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7

Population: PKS

Arm	Measure	Value (MEAN)	Dispersion
MMX Mesalamine (30mg/kg)	AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State	30942 ug*h/L	Standard Deviation 13743
MMX Mesalamine (60 mg/kg)	AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State	58119 ug*h/L	Standard Deviation 22729
MMX Mesalamine (100 mg/kg)	AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State	63067 ug*h/L	Standard Deviation 21752

Primary