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

NCT02431364 | Terminated Phase 1 Results

• 1 other identifier: KCP-335-701
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

KPT-335; Verdinexor; Karyopharm; First-in-Human; Adult Subjects

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. A serious adverse event (SAE) was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, was life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study.

  From start of study drug administration up to Day 33

Secondary Outcomes (14)

• Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) of Verdinexor

  Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose

• Area Under the Concentration-time Curve From Time Zero to Extrapolated to Infinity (AUC0-inf) of Verdinexor

  Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose

• Maximum Observed Concentration (Cmax) of Verdinexor

  Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose

• Average Plasma Concentration From Time Zero to 24 Hours Post-dose (Cavg0-24h) of Verdinexor

  Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24 hours post-dose

• Time of First Observation of Maximum Observed Concentration (Tmax) of Verdinexor

  Days 1 and 3: pre-dose, 15 minutes, 30 minutes, 1, 2, 3, 4, 8, 12, 24, 48 (only for Day 3) hours post-dose

Study Arms (5)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Verdinexor 5 mg

EXPERIMENTAL

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

Drug: Verdinexor

Verdinexor 10 mg

EXPERIMENTAL

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

Drug: Verdinexor

Verdinexor 20 mg

EXPERIMENTAL

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

Drug: Verdinexor

Verdinexor 40 mg

EXPERIMENTAL

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

Drug: Verdinexor

Interventions

Verdinexor DRUG

Participants received verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral

Also known as: KPT-335

Verdinexor 10 mg; Verdinexor 20 mg; Verdinexor 40 mg; Verdinexor 5 mg

Placebo OTHER

Participants received placebo matched to verdinexor; Dosage form: coated, immediate release Tablet; Route of administration: oral

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, Australia

Location

MeSH Terms

Interventions

verdinexor

Limitations and Caveats

This study was terminated due to administrative reasons.

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: May 1, 2015
• Study Start: May 26, 2015
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 20, 2023
• Results First Posted: April 13, 2021

Record last verified: 2023-01

Locations

AU (1)