Healthy
Conditions
Brief summary
This is a drug interaction study evaluating the pharmacokinetic profiles of Sulfamethoxazole administered alone & in combination with Multi MatriX system (MMX®) formulation of mesalazine/mesalazine (Lialda®; Mesavancol®; Mezavant®) (MMX Mesalazine/mesalamine).
Interventions
DRUGsulfamethoxazole + MMX placebo
800 mg sulfamethoxazole/160 mg trimethoprim twice daily (BID) + MMX Mesalazine/mesalamine placebo once daily (QD) orally for 3 days, then a single dose of 800 mg sulfamethoxazole/160 mg trimethoprim + single does of MMX Mesalazine/mesalamine placebo orally on Day 4.
DRUGSulfamethoxazole + MMX Mesalazine/mesalamine
800 mg sulfamethoxazole/160 mg trimethoprim BID + 4.8 g MMX Mesalazine/mesalamine QD for 3 days, then a single dose of 800 mg sulfamethoxazole/160 mg trimethoprim + a single dose of 4.8 g MMX Mesalazine/mesalamine on Day 4
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-55 years inclusive at the time of consent. The date of signing informed consent is defined as the beginning of the Screening Period. 2. Subject is willing to comply with any applicable contraceptive requirements of the protocol and is: * Male, or * Non-pregnant, non-lactating female * Females must be at least 90 days post-partum or nulliparous.
Exclusion criteria
1. A history of current or recurrent disease that could affect the colon. This includes gastrointestinal disease, peptic ulceration, gastrointestinal bleeding, celiac disease, lactose intolerance, ulcerative colitis, Crohn's disease, or Irritable Bowel Syndrome. Subjects who have a history of chronic constipation, which is physician diagnosed and treated, will also be excluded from the study (frequency of bowel movements \>48 hours between samples). 2. A history of current or relevant serious, severe, or unstable (acute or progressive) physical or psychiatric illness. 3. A history of gastrointestinal surgery performed within the past 12 months prior to the first dose of investigational product, with the exception of an appendectomy. 4. A history of or current clinically relevant moderate or severe renal or hepatic impairment. 5. A history of asthma or bronchospasm associated with the use of 5-ASA or other non-steroidal anti-inflammatory drugs. 6. Known or suspected intolerance or hypersensitivity to the investigational product or sulfamethoxazole/trimethoprim, closely related compounds, or any of the stated ingredients 7. A history of, or current, pancreatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve Within a Dosing Interval at Steady-State (AUCss) for Sulfamethoxazole | Assessed over a 24-hour period starting post-dose on day 4 | AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure of how much and how long a drug stays in a body. |
| Maximum Plasma Concentration at Steady-State (Cmaxss) for Sulfamethoxazole | Assessed over a 24-hour period starting post-dose on day 4 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sulfamethoxazole + MMX Placebo First 800 mg sulfamethoxazole/160 mg trimethoprim twice daily (BID) + MMX placebo once daily (QD) orally for 3 days and a single dose of 800 mg sulfamethoxazole/160 mg trimethoprim + single does of MMX placebo orally on Day 4 for first intervention; then 800 mg sulfamethoxazole/160 mg trimethoprim BID + 4.8 g MMX Mesalazine/mesalamine QD for 3 days and a single dose of 800 mg sulfamethoxazole/160 mg trimethoprim + a single dose of 4.8 g MMX Mesalazine/mesalamine on Day 4 for second intervention. | 22 |
| Sulfamethoxazole + MMX Mesalazine/Mesalamine First 800 mg sulfamethoxazole/160 mg trimethoprim BID + 4.8 g MMX Mesalazine/mesalamine QD for 3 days and a single dose of 800 mg sulfamethoxazole/160 mg trimethoprim + a single dose of 4.8 g MMX Mesalazine/mesalamine on Day 4 for first intervention; then 800 mg sulfamethoxazole/160 mg trimethoprim twice daily (BID) + MMX placebo once daily (QD) orally for 3 days and a single dose of 800 mg sulfamethoxazole/160 mg trimethoprim + single does of MMX placebo orally on Day 4 for second intervention. | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Unacceptable behavior | 0 | 1 |
| Second Intervention | Incarcerated | 1 | 0 |
Baseline characteristics
| Characteristic | Sulfamethoxazole + MMX Placebo First | Sulfamethoxazole + MMX Mesalazine/Mesalamine First | Total |
|---|---|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 11.7 | 35.4 years STANDARD_DEVIATION 12.6 | 36.7 years STANDARD_DEVIATION 12 |
| Age, Customized 18 to 55 years of age | 22 Participants | 22 Participants | 44 Participants |
| Region of Enrollment United States | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 43 | 14 / 44 |
| serious Total, serious adverse events | 0 / 43 | 0 / 44 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve Within a Dosing Interval at Steady-State (AUCss) for Sulfamethoxazole
AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure of how much and how long a drug stays in a body.
Time frame: Assessed over a 24-hour period starting post-dose on day 4
Population: Pharmacokinetic Analysis Set defined as all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set defined as subjects who took at least 1 dose of investigational product and had at least 1 postdose safety assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sulfamethoxazole + MMX Placebo | Area Under the Plasma Concentration Versus Time Curve Within a Dosing Interval at Steady-State (AUCss) for Sulfamethoxazole | 786 h*ug/ml | Standard Deviation 169 |
| Sulfamethoxazole + MMX Mesalazine/Mesalamine | Area Under the Plasma Concentration Versus Time Curve Within a Dosing Interval at Steady-State (AUCss) for Sulfamethoxazole | 909 h*ug/ml | Standard Deviation 198 |
90% CI: [1.12, 1.18]ANOVA
Primary
Maximum Plasma Concentration at Steady-State (Cmaxss) for Sulfamethoxazole
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 frame: Assessed over a 24-hour period starting post-dose on day 4
Population: Pharmacokinetic Analysis Set defined as all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set defined as subjects who took at least 1 dose of investigational product and had at least 1 postdose safety assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sulfamethoxazole + MMX Placebo | Maximum Plasma Concentration at Steady-State (Cmaxss) for Sulfamethoxazole | 89.1 ug/ml | Standard Deviation 16.3 |
| Sulfamethoxazole + MMX Mesalazine/Mesalamine | Maximum Plasma Concentration at Steady-State (Cmaxss) for Sulfamethoxazole | 100 ug/ml | Standard Deviation 20.2 |
90% CI: [1.09, 1.15]ANOVA