Open-label PK Study to Evaluate Lansoprazole and Neratinib in Healthy Subjects

NCT02334501 | Completed Phase 1

• 1 other identifier: PUMA-NER-0101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, 2-period, fixed-sequence study in 15 healthy adult subjects under fed conditions. To evaluate the effect of multiple doses of lansoprazole on the absorption and pharmacokinetics (PK) of a single dose of neratinib in healthy subjects.

Conditions

Healthy

Keywords

Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• AUC(0-t) of neratinib with and without lansoprazole

  The area under the plasma concentration-time curve, from time 0 to the last measurable nonzero concentration, as calculated by the linear trapezoidal method.

  0, 0.5, 1, 2, 2.75, 3.5, 4.25, 5, 5.75, 6.5, 7.25, 8, 10, 12, 24, 32, 48, 60, and 72 hours post-dose

• AUC(0-inf) of neratinib with and without lansoprazole

  The area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC(0-inf) is calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant.

  0, 0.5, 1, 2, 2.75, 3.5, 4.25, 5, 5.75, 6.5, 7.25, 8, 10, 12, 24, 32, 48, 60, and 72 hours post-dose

• Cmax of neratinib with and without lansoprazole

  Maximum observed concentration.

  0, 0.5, 1, 2, 2.75, 3.5, 4.25, 5, 5.75, 6.5, 7.25, 8, 10, 12, 24, 32, 48, 60, and 72 hours post-dose

Secondary Outcomes (1)

• Number of participants with adverse events

  over 4 week study period

Study Arms (1)

Treatment A (Period 1) and Treatment B (Period 2)

EXPERIMENTAL

Treatment A (240mg Neratinib x1) Treatment B (30mg Lansoprazole X 7 days + 240mg Neratinib x1)

Drug: Lansoprazole; Drug: Neratinib

Interventions

Lansoprazole DRUG

Treatment A (Period 1) and Treatment B (Period 2)

Neratinib DRUG

Treatment A (Period 1) and Treatment B (Period 2)

Eligibility Criteria

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

You may qualify if:

• Healthy, adult, men or women, 18 to 55 years of age, inclusive, at screening. Body Mass Index ≥ 18.5 and ≤ 32.0 kg/m2 at screening. Non to moderate smokers (up to 10 cigarettes a day for at least 3 months prior to screening).
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or 12-lead electrocardiograms (ECGs), as deemed by the principal investigator (PI).
• Women of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and for at least 28 days following the last dose or be using one of the protocol-specific birth control methods.

You may not qualify if:

• Acute disease state (eg, nausea, vomiting, fever, or diarrhea) within 7 days prior to the first dose of study drug.
• History or presence of alcoholism or drug abuse within the past 2 years prior to screening.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (eg, proton-pump inhibitors \[PPIs\]).
• Women who are pregnant or lactating. Positive results at screening for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus.
• Unable to refrain from or anticipates the use of:
• Any drug, including prescription and nonprescription medications, herbal remedies, or vitamin supplements (including proton-pump inhibitors) beginning 14 days prior to the first dose of study drug and throughout the study. Acetaminophen (up to 2 g per 24 hour period) and/or loperamide (up to 6 mg per 24 hours) may be permitted during the study at the direction of the PI.
• Any drugs known to be significant inducers of cytochrome p450 enzymes and/or P glycoprotein, including St. John's Wort, for 28 days prior to the first dose of study drug and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/pharmacodynamics interaction with study drug.

Sponsors & Collaborators

• Puma Biotechnology, Inc.: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Lansoprazole; neratinib

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 Design

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

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: January 8, 2015
• Study Start: August 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: May 11, 2016

Record last verified: 2016-05

Locations

US (1)