TAK-438_110 Drug Interaction With Cytochrome P450 3A4 (CYP3A4) Inhibitor Clarithromycin

NCT02774902 | Completed Phase 1

• 3 other identifiers: TAK-438-1102010-020813-10U1111-1181-8324
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the effect of multiple oral doses of clarithromycin on the pharmacokinetics of TAK-438 and its metabolites in healthy male adult participants following a single oral dose of TAK-438.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (4)

• Cmax: Maximum Observed Plasma Concentration for TAK-438 and TAK-438 Metabolites (M-I, M-II, M-III, M-IV-Sul)

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

• AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438 and TAK-438 Metabolites (M-I, M-II, M-III, M-IV-Sul)

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

• AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-438 and TAK-438 Metabolites (M-I, M-II, M-III, M-IV-Sul)

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

• AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-438 and TAK-438 Metabolites (M-I, M-II, M-III, M-IV-Sul)

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

Secondary Outcomes (10)

• Ratio of TAK-438 Metabolites Cmax to TAK-438 Cmax

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

• Ratio of TAK-438 Metabolites AUClast to TAK-438 AUClast

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

• Ratio of TAK-438 Metabolites AUC∞ to TAK-438 AUC∞

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

• Ratio of TAK-438 Metabolites AUC(0-24) to TAK-438 AUC(0-24)

  Days 1 and 8 pre-dose and at multiple timepoints (up to 48 hours) post-dose

• Predose Observed Plasma Concentration of Clarithromycin

  Days 3 to 9 pre-dose (-1 hours [1 hour before TAK-438 dosing]) and (11 hours [11 hours after TAK 438 dosing])

Study Arms (1)

TAK-438 40 mg + Clarithromycin 500 mg

EXPERIMENTAL

TAK-438 40 mg, tablets, orally once on Days 1 and 8 along with clarithromycin 500 mg, tablets, orally twice daily from Days 3 to 9.

Drug: TAK-438; Drug: Clarithromycin

Interventions

TAK-438 DRUG

TAK-438 tablets

TAK-438 40 mg + Clarithromycin 500 mg

Clarithromycin DRUG

Clarithromycin tablets

TAK-438 40 mg + Clarithromycin 500 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In the opinion of the investigator the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Is a healthy adult male participant, of non-Japanese origin.
• Is aged 18 to 45 years, inclusive, at the time of informed consent and first study medication dose.
• Weighs at least 45 kg and has a body mass index (BMI) between 18 and 30 kg/m\^2, inclusive at Screening.
• A male participant who is sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.

You may not qualify if:

• Is willing to abstain from caffeine and alcohol from 72 hours before first dose (Day 1) until the Follow-up call.
• Is willing to abstain from strenuous exercise from 72 hours before first dose (Day 1) until the Follow-up call.
• Is willing to provide a sample for pharmacogenomic analysis.
• Has received any investigational compound within 90 days prior to the first dose on Day 1.
• Has received TAK-438 in a previous clinical study or as a therapeutic agent.
• Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has a known hypersensitivity or allergies to clarithromycin or any associated excipients.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Has taken or is required to take any excluded medication.
• Intends to donate sperm during the course of this study or for 12 weeks thereafter.
• Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-438, or a similar drug in the same class, or clarithromycin, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
• Has a history or clinical manifestations of significant symptomatic, gastroesophageal reflux disease (GERD), erosive esophagitis (EE), duodenal ulcer, gastric ulcer, dyspepsia, Barrett esophagus (BE), or Zollinger-Ellison syndrome.
• Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, EE frequent \[more than once per week\], occurrence of heartburn, or any surgical intervention \[eg, cholecystectomy\]).
• Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.
• Has a positive test result for hepatitis A, hepatitis B surface antigen, antibody to hepatitis C virus, or human immunodeficiency virus at Screening.

Sponsors & Collaborators

• Takeda: lead

Related Publications (1)

• Jenkins H, Jenkins R, Patat A. Effect of Multiple Oral Doses of the Potent CYP3A4 Inhibitor Clarithromycin on the Pharmacokinetics of a Single Oral Dose of Vonoprazan: A Phase I, Open-Label, Sequential Design Study. Clin Drug Investig. 2017 Mar;37(3):311-316. doi: 10.1007/s40261-016-0488-6.

  PMID: 27928738 DERIVED

MeSH Terms

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; Clarithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: May 17, 2016
• Study Start: August 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: May 17, 2016

Record last verified: 2016-05