Drug-drug Interaction Study to Evaluate the Effect of Omeprazole on CG5503 (Tapentadol)

NCT03979989 | Completed Phase 1

• 2 other identifiers: HP5503/20R331333-PAI-1009
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This was a single center, open-label, two-way crossover, drug-drug-interaction study to determine the effect of multiple dosing of omeprazole on 4 consecutive days on the pharmacokinetics of a single dose of an immediate-release capsule of CG5503 (tapentadol) in healthy participants.

Conditions

Pharmacokinetic

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic parameter: Cmax of CG5503 base

  14 blood samples for the determination of serum concentrations were taken at pre-dose and up to 48 hours after administration of the CG5503 IR capsule. The evaluation of the maximum observed serum concentration (Cmax) was based on the CG5503 base concentrations measured in serum samples using a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method.

  Pre-dose up to 48 hours post-dose

• Pharmacokinetic parameter: AUC0-t of CG5503 base

  14 blood samples for the determination of serum concentrations were taken at pre-dose and up to 48 hours after administration of the CG5503 IR capsule. The evaluation of the area under the concentration time curve (AUC) from 0 hours to time t (=48 hours) (AUC0-t) was based on the CG5503 base concentrations measured in serum samples.

  Pre-dose up to 48 hours post-dose

• Pharmacokinetic parameter: AUC0-inf of CG5503 base

  14 blood samples for the determination of serum concentrations were taken at pre-dose and up to 48 hours after administration of the CG5503 IR capsule. The AUC from 0 hours to infinity (AUC0-inf) was extrapolated from the AUC from administration to the last measured concentration.

  Pre-dose up to 48 hours post-dose

Secondary Outcomes (4)

• Pharmacokinetic parameter: Cmax of CG5503-O-glucuronide

  Pre-dose up to 48 hours post-dose

• Pharmacokinetic parameter: AUC0-t of CG5503-O-glucuronide

  Pre-dose up to 48 hours post-dose

• Pharmacokinetic parameter: AUC0-inf of CG5503-O-glucuronide

  Pre-dose up to 48 hours post-dose

• Incidence of treatment emergent adverse events

  Day 1 to Day 4

Study Arms (2)

Tapentadol IR

EXPERIMENTAL

A single oral dose of tapentadol IR was administered in a fasted state (Treatment A).

Drug: Tapentadol IR capsule

Omeprazole, Tapentadol IR

EXPERIMENTAL

Oral doses of omeprazole were administered once daily in a fasted state on 4 consecutive days (Days -3 to 1), plus 1 capsule of CG5503 IR administered 2 hours after the administration of omeprazole on Day 1 (Treatment B).

Drug: Tapentadol IR capsule; Drug: Omeprazole capsule

Interventions

Tapentadol IR capsule DRUG

Tapentadol IR capsule containing 93 mg tapentadol hydrochloride.

Omeprazole, Tapentadol IR; Tapentadol IR

Omeprazole capsule DRUG

Omeprazole capsule containing 40 mg omeprazole.

Omeprazole, Tapentadol IR

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Man or woman, between 25 and 55 years of age, inclusive.
• Body mass index between 20 and 28 kg/square meter, inclusive, with a minimum body weight of 50 kg.
• Signed the informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Women must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile, abstinent, or practicing or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study (effective methods of birth control include prescription hormonal contraceptives, intrauterine devices, double-barrier method, and male partner sterilization). Women must have a negative serum beta-human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test on Day -1 of Treatment Period 1.
• Healthy on the basis of pre-study physical examination, medical history, 12-lead electrocardiogram, vital signs, and clinical laboratory parameters (serum chemistry, serology, hematology, and urinalysis) performed within 21 days before administration of the first dose of study drug. NOTE: If the results of the chemistry, hematology, or urinalysis testing are not within the normal limits of the laboratory reference ranges, the participant may be included in the study only on the condition that the investigator judges the deviations not clinically relevant.
• Signed informed consent for pharmacogenomic testing indicating whether they do or do not wish to participate in the genetic part of the study. NOTE: Participation in the genetic testing component is not mandatory for participation in the study.
• Blood pressure (after the subject is supine for 5 minutes) between 100 and 140 mmHg systolic, inclusive, and 50 and 90 mmHg diastolic, inclusive.
• Are willing to follow the prohibitions and restrictions as specified in the protocol.

You may not qualify if:

• History of
• seizure disorder or epilepsy, or
• mild or moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm within 1 year of screening, or
• severe traumatic brain injury (consisting of one or more of the following: brain contusion; intracranial hematoma; or episode(s) of more than 24 hours duration of unconsciousness or post-traumatic amnesia) within 15 years of screening, or
• severe traumatic brain injury resulting in ongoing sequelae consisting of transient changes in consciousness or symptoms suggestive thereof at any time.
• History of clinically significant pulmonary, gastrointestinal, immunologic, endocrine, neurologic, psychiatric, thromboembolic disease or metabolic disturbances, or any current physical conditions that could interfere with the interpretation of the study results.
• History of clinically significant allergies, especially known hypersensitivity or intolerance to opioids, opioid antagonists (e.g., naloxone), benzodiazepines (e.g., diazepam, clonazepam, lorazepam), or any study drug formulation component or any of the excipients, or heparin (should the use of a heparin lock be necessary).
• Positive test for human immunodeficiency virus (HIV 1 and 2), hepatitis B, or hepatitis C.
• History of substance abuse or a positive test for drugs of abuse or alcohol at screening (including on the day before the initial administration of study drug in the first treatment period).
• Blood donation or acute loss of blood (more than 500 mL) during the 3 months before study drug administration or intention to donate blood or blood products during the study or within 1 month after the completion of the study.
• Women who are pregnant, or plan to become pregnant during the study, or who are breast-feeding.
• Participants for whom omeprazole treatment is contraindicated.
• Participants who have used or plan to use the following during the study:
• prescription medication (except for birth control medications and hormone replacement therapy) within 14 days before the first study drug administration
• monoamine-oxidase inhibitors (MAOIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) within 21 days before the first study drug administration

Sponsors & Collaborators

• Grünenthal GmbH: lead
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: collaborator

Study Sites (1)

J&JPRD Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Study Director Grünenthal

  Grünenthal GmbH

  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

Model Details: Participants were randomized to 1 of 2 treatment sequences (AB or BA). There was a washout of at least 7 days between the CG5503 administrations.

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 10, 2019
• Study Start: September 28, 2005
• Primary Completion: November 16, 2005
• Study Completion: November 16, 2005
• Last Updated: June 10, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)