A Study Investigating the Effect of Food and Esomeprazole on the Single Oral Dose Pharmacokinetics of RO5424802 in Healthy Volunteers.

Healthy Volunteer Clinical Trial

Official title:

AN OPEN-LABEL, TWO GROUP STUDY TO INVESTIGATE THE EFFECT OF FOOD (GROUP 1) AND ESOMEPRAZOLE (GROUP 2) ON THE SINGLE ORAL DOSE PHARMACOKINETICS OF RO5424802 IN HEALTHY SUBJECTS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02023125
• Other study ID #: NP28991
• Status: Completed
• Phase: Phase 1
• First received: December 23, 2013
• Last updated: July 1, 2016
• Start date: January 2014
• Est. completion date: February 2014

Study information

• Verified date: July 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This two-group study will investigate the effect of food (group 1) and esomeprazole (group 2) on the single oral dose pharmacokinetics of RO5424802 in healthy volunteers.

Participants in Group 1 will be randomly assigned to a two period treatment sequence (AB or BA) in which they will receive a single, oral dose of RO5424802 per period separated by at least 10 days. Each subject will receive single, oral doses RO5424802 given under fasted conditions (Treatment A) or following the ingestion of a high fat, high calorie meal (Treatment B) as determined by their assigned sequence.

Participants in Group 2 will be given a single, oral dose of RO5424802 following a standard meal. After a washout period of at least 10 days, they will receive an oral dose of esomeprazole (40 mg) once daily for 6 days. On the 6th day of esomeprazole administration, a single, oral dose RO5424802 will be given after ingestion of a standard meal.

In all groups, pharmacokinetics will be assessed in the 4 days following RO5424802 administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 18 to 55 years of age, inclusive.

• Body mass index (BMI) between 18 to 32 kg/m2 inclusive.

• Healthy male and female volunteers. Healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis.

• Female subjects must be surgically sterile or post-menopausal for the past year confirmed by a blood follicle stimulating hormone (FSH) test for females without hormone replacement therapy (HRT).

• Male subjects must be willing to use effective contraception, as defined by the protocol, throughout the study and for 3 months after last drug administration.

• Willing to abstain from xanthine-containing beverages or food (coffee, tea, cola, chocolate, and "energy drinks") use from 72 hours prior to admission to the study clinic until discharge.

• Willing to abstain from consuming grapefruit, pomelo, star fruit, or Seville orange containing products from 7 days prior to first dose of study medication through discharge.

• Willing to avoid prolonged sun exposure while taking RO5424802 and through follow-up. Subjects should also be advised to use a broad spectrum sun screen and lip balm of at least sun protection factor (SPF) > 30 to help protect against potential sunburn.

• Group 2 participants should be H. Pylori negative via breath test.

Exclusion Criteria:

• Pregnant or breastfeeding women, males with female partners who are pregnant or breastfeeding, or women of childbearing potential.

• Positive test for drugs of abuse, alcohol or cotinine test at screening or prior to admission to the study unit.

• Suspicion of regular consumption of drug(s) of abuse including marijuana.

• Current smokers or subjects who have discontinued smoking less than six months prior to first dosing. Subjects should avoid smoky environments for at least 1 weeks prior to each cotinine test.

• History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption will be prohibited 72 hours prior to admission to the study clinic and throughout the entire study until discharge.

• Participants with any risk factors or family history for QT/QTcF prolongation or ECG abnormalities or any abnormality in the ECG that, in the opinion of the investigator, increases the risk of participating in the study.

• Confirmed systolic blood pressure (SBP) greater than 140 mmHG or less than 90 mmHg or diastolic blood pressure (DBP) greater than 90 mmHg or less than 45 mmHg at screening, admission to the study center or prior to dosing.

• Notable resting bradychardia (mean pulse rate < 45 bpm) or tachycardia (mean pulse rate > 90 bpm).

• Use of any medications (prescription or over-the-counter) within 2 weeks or 5 half-lives (whichever is longer) before the first dose of the study medication with the exception of acetaminophen up to 2 g per day up to 48 hours prior to dosing, not to exceed 4 g total during the week prior to dosing.

• Use of any herbal supplements or any metabolic inducers within 4 weeks or 5 half-lives (whichever is longer) before the first dose of study medication, including but not limited to the following drugs: rifampin, rifabutin, glucocorticoids, carbamazepine, phenytoin and phenobarbital.

• Strenuous activity, sunbathing or contact sports are not allowed from 4 days prior to entry into the clinical site and for the duration of the study until follow-up.

• Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever is longer) or 6 months for biologic therapies prior to first dosing.

• Donation of blood over 450 mL within 45 days prior to screening.

• Regular use of antacids, H-2 receptor blockers, PPIs or any medications which may alter the normal gastric environment and/or motility. No use of such medications within 2 weeks prior to first dose.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Other:
• Hight fat and calorie meal
High fat and calorie meal served prior to RO5424802 administration

Drug:
• RO5424802
Single oral dose

Other:
• Standard meal
Standard meal served prior to RO5424802 administration

Drug:
• esomeprazole
40 mg esomeprazole administered daily for 6 days prior to RO5424802 administration

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma area under the concentration-time curve (AUC) of RO5424802		Up to Day 20	No
Secondary	Incidence of adverse events		Up to 60 days	No
Secondary	Plasma AUC of major metabolite after RO5424802 administration		Up to Day 20	No