Trial of Safety and Tolerability of Oral Verdinexor (KPT-335) in Healthy Adults

Karyopharm Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Healthy

Treatments: Other: Placebo; Drug: Verdinexor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02431364

KCP-335-701

Details and patient eligibility

About

This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and 3 to healthy adult participants.

Full description

This is a randomized, double-blind, sequential, dose-escalation, Phase 1 trial to evaluate the safety and tolerability of verdinexor. Verdinexor or placebo will be given on Days 1 and 3 to healthy adult participants.

Cohorts of 8 participants each (6 active, 2 placebo) will be sequentially administered verdinexor or placebo (one dose on Day 1 and one dose on Day 3) using a dose-escalation scheme. A conservative, sequential, dose-escalation strategy employing decreasing escalation increments will be used.

Enrollment: 33 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants must be in good health as determined by the investigator, based on the medical history, ECG, physical examination, and safety laboratory tests at screening.
• Participants must be identified as a non-smoker at the screening visit (a non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to the screening visit and who has a ≤ 15 pack year history of lifetime cigarette use). A urine cotinine test will be performed at screening and at the time of clinic check-in prior to study drug treatment.

Exclusion criteria

• The participant has any surgical or medical condition that potentially may alter the absorption, metabolism, or excretion of the study drug such as gastrectomy, Crohn's disease, or liver disease.
• The participant has a history of clinically significant allergies. Hay fever is allowed unless it is active or has required treatment within the previous 2 months.
• Presence of a chronic condition(s) with clinical or historical evidence of recent exacerbation, or other information to suggest non-control of such condition(s).
• History of alcohol abuse or drug addiction within 12 months of the screening visit.
• Any participant with active cataracts or medical history of cataracts.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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33 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received matched placebo tablets to verdinexor tablets orally once daily on Days 1 and 3.

Treatment:

Other: Placebo

Verdinexor 5 mg

Experimental group

Description:

Participants received verdinexor 5 milligrams (mg) (2 tablets of 2.5 mg each) orally once daily on Days 1 and 3.

Treatment:

Drug: Verdinexor

Verdinexor 10 mg

Experimental group

Description:

Participants received verdinexor 10 mg tablet orally once daily on Days 1 and 3.

Treatment:

Drug: Verdinexor

Verdinexor 20 mg

Experimental group

Description:

Participants received verdinexor 20 mg tablet (2 tablets of 10 mg each) orally once daily on Days 1 and 3.

Treatment:

Drug: Verdinexor

Verdinexor 40 mg

Experimental group

Description:

Participants received verdinexor 40 mg tablet (4 tablets of 10 mg each) orally once daily on Days 1 and 3.

Treatment:

Drug: Verdinexor