Healthy
Conditions
Brief summary
This is a drug interaction study evaluating the pharmacokinetic profiles of amoxicillin administered alone & in combination with MMX Mesalazine/mesalamine.
Interventions
DRUGAmoxicillin + MMX placebo
MMX placebo administered once a day (QD) orally on Days 1-3, then a single oral dose of Amoxicillin (500 mg) + MMX placebo on Day 4.
DRUGAmoxicillin + MMX mesalazine/mesalamine
MMX mesalazine/mesalamine (4.8 g) administered QD orally on Days 1-3, then a single oral dose of Amoxicillin (500 mg) + MMX mesalazine/mesalamine (4.8 g) 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 amoxicillin, 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 From Time Zero to Infinity (AUC 0→∞) for Amoxicillin | 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 how much and how long a drug stays in a body. |
| Maximum Plasma Concentration (Cmax) for Amoxicillin | 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 |
|---|---|
| Amoxicillin + MMX Placebo First MMX placebo administered once a day (QD) orally on Days 1-3, then a single oral dose of Amoxicillin (500 mg) + MMX placebo on Day 4 for first intervention. Then, MMX mesalazine/mesalamine (4.8 g) administered QD orally on Days 1-3, then a single oral dose of Amoxicillin (500 mg) + MMX mesalazine/mesalamine (4.8 g) on Day 4 for second intervention. | 31 |
| Amoxicillin + MMX Mesalazine/Mesalamine First MMX mesalazine/mesalamine (4.8 g) administered QD orally on Days 1-3, then a single oral dose of Amoxicillin (500 mg) + MMX mesalazine/mesalamine (4.8 g) on Day 4 for first intervention. Then, MMX placebo administered once a day (QD) orally on Days 1-3, then a single oral dose of Amoxicillin (500 mg) + MMX placebo on Day 4 for second intervention. | 31 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | subject incarcerated | 1 | 0 |
| First Intervention | Withdrawal by Subject | 1 | 0 |
| Second Intervention | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Amoxicillin + MMX Mesalazine/Mesalamine First | Amoxicillin + MMX Placebo First |
|---|---|---|---|
| Age, Continuous | 32.2 years STANDARD_DEVIATION 10.3 | 30.1 years STANDARD_DEVIATION 8.91 | 34.3 years STANDARD_DEVIATION 11.2 |
| Age, Customized Between 18 and 55 years | 62 Participants | 31 Participants | 31 Participants |
| Region of Enrollment United States | 62 Participants | 31 Participants | 31 Participants |
| Sex: Female, Male Female | 16 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 46 Participants | 22 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 | 9 / 62 | 13 / 59 |
| serious Total, serious adverse events | 0 / 62 | 0 / 59 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC 0→∞) for Amoxicillin
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: Assessed over a 24-hour period starting post-dose on day 4
Population: The Pharmacokinetic Analysis Set was defined as all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. The Safety Analysis Set consisted of subjects who took at least 1 dose of investigational product and had at least 1 postdose safety assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin + MMX Placebo | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC 0→∞) for Amoxicillin | 27.8 h*ug/ml | Standard Deviation 5.02 |
| Amoxicillin + MMX Mesalazine/Mesalamine | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC 0→∞) for Amoxicillin | 28.3 h*ug/ml | Standard Deviation 6.37 |
90% CI: [0.995, 1.04]ANOVA
Primary
Maximum Plasma Concentration (Cmax) for Amoxicillin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin + MMX Placebo | Maximum Plasma Concentration (Cmax) for Amoxicillin | 10.3 ug/ml | Standard Deviation 2.59 |
| Amoxicillin + MMX Mesalazine/Mesalamine | Maximum Plasma Concentration (Cmax) for Amoxicillin | 10.2 ug/ml | Standard Deviation 2.89 |
90% CI: [0.94, 1.04]ANOVA