Pharmacokinetics Study of Oral Rivaroxaban in Healthy Participants

NCT01464450 | Completed Phase 1

• 2 other identifiers: CR100688RIVAROXNAP1001
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to learn about the relative bioavailability (the extent to which the drug becomes available to the body) and pharmacokinetics (blood levels) of rivaroxaban in healthy participants after receiving a 20 mg rivaroxaban tablet orally as a whole tablet, crushed and mixed in applesauce, and as a suspension through a Naso-gastric (NG) tube. The relative bioavailability of rivaroxaban may be different when given as a crushed tablet compared with an intact (whole) tablet and when given via an NG tube. The safety and tolerability of rivaroxaban will also be assessed.

Conditions

Pharmacokinetics; Bioavailability; Healthy Participants

Keywords

Pharmacokinetics; Bioavailability; Healthy Participants

Outcome Measures

Primary Outcomes (1)

• Rivaroxaban plasma concentrations

  Approximately 30 days

Secondary Outcomes (7)

• The number of patients with adverse events reported

  Up to approximately 60 days

• Change from baseline in coagulation tests (prothrombin time [PT] and partial thromboplastin time [PTT])

  Baseline and at approximately 47 days

• Change from baseline in Electrocardiograms (ECGs)

  Baseline and at approximately 47 days

• Number of participants with abnormal vital signs

  Baseline and at approximately 10 days, 20 days and 30 days

• Number of participants with changes in physical examinations

  Baseline and at approximately 10 days, 20 days and 30 days

Study Arms (6)

Sequence 1: Treatment A - B - C

ACTIVE COMPARATOR

Participants will receive a single 20 mg-dose of rivaroxaban as a whole tablet swallowed intact with 70 mL of applesauce and 130 mL of water followed by a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 1 (Treatment A,) followed by a single 20 mg-dose of rivaroxaban crushed and mixed in 70 ml of applesauce, followed by 2 mortar rinses of 65 mL each of water (to ensure delivery of the entire dose) and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 2 (Treatment B) and followed by 20 mL of water via NG tube (to prime and pre-wet the lumen), followed by a single 20 mg-dose of rivaroxaban crushed and suspended in 50 mL of water given via NG tube, followed by 2 mortar rinses of 65 mL each of water and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 3 (Treatment C.)

Drug: Rivaroxaban

Sequence 2: Treatment A - C - B

ACTIVE COMPARATOR

Participants will receive a single 20 mg-dose of rivaroxaban as a whole tablet swallowed intact with 70 mL of applesauce and 130 mL of water followed by a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 1 (Treatment A,) followed by 20 mL of water via NG tube (to prime and pre-wet the lumen), followed by a single 20 mg-dose of rivaroxaban crushed and suspended in 50 mL of water given via NG tube, followed by 2 mortar rinses of 65 mL each of water and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 2 (Treatment C) and followed by a single 20 mg-dose of rivaroxaban crushed and mixed in 70 ml of applesauce, followed by 2 mortar rinses of 65 mL each of water (to ensure delivery of the entire dose) and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 3 (Treatment B.)

Drug: Rivaroxaban

Sequence 3: Treatment B - C - A

ACTIVE COMPARATOR

Participants will receive a single 20 mg-dose of rivaroxaban crushed and mixed in 70 ml of applesauce, followed by 2 mortar rinses of 65 mL each of water (to ensure delivery of the entire dose) and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 1 (Treatment B,) followed by a single 20 mg-dose of rivaroxaban crushed and suspended in 50 mL of water given via NG tube, followed by 2 mortar rinses of 65 mL each of water and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 2 (Treatment C) and followed by a single 20 mg-dose of rivaroxaban as a whole tablet swallowed intact with 70 mL of applesauce and 130 mL of water followed by a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 3 (Treatment A.)

Drug: Rivaroxaban

Sequence 4: Treatment B - A - C

ACTIVE COMPARATOR

Participants will receive a single 20 mg-dose of rivaroxaban crushed and mixed in 70 ml of applesauce, followed by 2 mortar rinses of 65 mL each of water (to ensure delivery of the entire dose) and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 1 (Treatment B,) followed by a single 20 mg-dose of rivaroxaban as a whole tablet swallowed intact with 70 mL of applesauce and 130 mL of water followed by a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 2 (Treatment A) and followed by 20 mL of water via NG tube (to prime and pre-wet the lumen), followed by a single 20 mg-dose of rivaroxaban crushed and suspended in 50 mL of water given via NG tube, followed by 2 mortar rinses of 65 mL each of water and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 3 (Treatment C.)

Drug: Rivaroxaban

Sequence 5: Treatment C - A - B

ACTIVE COMPARATOR

Participants will receive a single 20 mg-dose of rivaroxaban crushed and suspended in 50 mL of water given via NG tube, followed by 2 mortar rinses of 65 mL each of water and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 1 (Treatment C,) followed by a single 20 mg-dose of rivaroxaban as a whole tablet swallowed intact with 70 mL of applesauce and 130 mL of water followed by a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 2 (Treatment A) and followed by and followed by a single 20 mg-dose of rivaroxaban crushed and mixed in 70 ml of applesauce, followed by 2 mortar rinses of 65 mL each of water (to ensure delivery of the entire dose) and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 3 (Treatment B.)

Drug: Rivaroxaban

Sequence 6: Treatment C - B - A

ACTIVE COMPARATOR

Participants will receive a single 20 mg-dose of rivaroxaban crushed and suspended in 50 mL of water given via NG tube, followed by 2 mortar rinses of 65 mL each of water and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 1 (Treatment C,) followed by and followed by a single 20 mg-dose of rivaroxaban crushed and mixed in 70 ml of applesauce, followed by 2 mortar rinses of 65 mL each of water (to ensure delivery of the entire dose) and a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 2 (Treatment B) and followed by a single 20 mg-dose of rivaroxaban as a whole tablet swallowed intact with 70 mL of applesauce and 130 mL of water followed by a liquid meal (100 mL of Osmolite® 1.5 Cal at 0, 0.5, 1, 1.5 and 2 hours after receiving the study drug) in Period 3 (Treatment A.)

Drug: Rivaroxaban

Interventions

Rivaroxaban DRUG

Single 20 mg-dose

Sequence 1: Treatment A - B - C; Sequence 2: Treatment A - C - B; Sequence 3: Treatment B - C - A; Sequence 4: Treatment B - A - C; Sequence 5: Treatment C - A - B; Sequence 6: Treatment C - B - A

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy on the basis of physical examination, medical history, clinical laboratory tests, vital signs, and 12-lead Electrocardiogram (ECG) performed at screening; Non-smoker for at least 3 months before screening; Women must be postmenopausal, surgically sterile or practicing a highly effective method of birth control; Men must agree to use birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug; Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg.; Be willing and able to adhere to the prohibitions and restrictions specified in this protocol;

You may not qualify if:

• History of or current clinically significant medical illness; Allergies, hypersensitivity, or intolerance to any component of rivaroxaban or its excipients or to Osmolite® 1.5 Cal; Contraindications to the use of anticoagulant (a drug used to thin blood) therapy (eg, bleeding diathesis, history of gastrointestinal (GI) bleeding within 1 year or coagulopathy); History of any disorder known to increase the risk of bleeding; Hepatic dysfunction and/or elevated serum transaminases; Clinically relevant hepatosplenomegaly as determined by the study investigator; Renal insufficiency; History of malignancy within 2 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence); Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 1 month before the planned first dose of study drug; Any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments; Had major surgery, (eg, requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or planned surgery during the time the subject is expected to participate in the study or within 12 weeks after the last dose of study agent is given; Uses any prescription or nonprescription medication (including vitamins and herbal supplements), except for (with restrictions) acetaminophen, oral contraceptives, and hormonal replacement therapy (stable dose) within 14 days before the first dose of the study drug is scheduled up to be given up to the End of Study/Early Withdrawal; History of drug or alcohol abuse within the past 2 years or a positive test for drugs of abuse at screening; Donated blood or blood products or had substantial loss of blood (more than 500 mL) within 3 months before receiving the study drug or intention or donation of blood or blood products within 1 month before receiving the study drug, during the study or within 1 month after the completion of the study; Unable to swallow solid, oral dosage forms whole with the aid of water, crushed forms mixed with apple sauce or tolerate placement of a NG tube for delivery of drug suspension; Has a history of testing positive for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies.

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead
• Bayer: collaborator

Study Sites (1)

Unknown Facility

Neptune City, New Jersey, United States

Location

MeSH Terms

Interventions

Rivaroxaban

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2011
• First Posted: November 3, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 24, 2017

Record last verified: 2017-01

Locations

US (1)