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

Purpose

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 subjects.

Condition	Intervention	Phase
Healthy	Drug: Verdinexor Other: Placebo	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Investigator) Primary Purpose: Basic Science
Official Title:	A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential, Dose-Escalating Trial to Evaluate the Safety and Tolerability of Oral Verdinexor (KPT-335) in Healthy Adult Subjects

Further study details as provided by Karyopharm Therapeutics Inc:

Primary Outcome Measures:

Safety and tolerability measured by incidence of adverse events [ Time Frame: 46 days ]
Safety and tolerability will be evaluated through treatment emergent adverse events (TEAEs), physical examinations, vital signs, electrocardiograms (ECGs), supportive care medications, and changes in laboratory parameters (chemistry, hematology, and urinalysis).

Secondary Outcome Measures:

Maximum plasma concentration (Cmax) [ Time Frame: 46 days ]
Maximum Tolerated Dose (MTD) Determination [ Time Frame: 46 days ]
Area under the curve from 0 to 24 hours post-dose (AUC(0-24) [ Time Frame: 24 hours ]


Enrollment:	32
Study Start Date:	May 2015
Study Completion Date:	October 2015
Primary Completion Date:	October 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 5 mg verdinexor on Days 1 and 3 or Placebo	Drug: Verdinexor Other Name: KPT-335 Other: Placebo
Experimental: Cohort 2 10 mg verdinexor on Days 1 and 3	Drug: Verdinexor Other Name: KPT-335
Experimental: Cohort 3 20 mg verdinexor on Days 1 and 3	Drug: Verdinexor Other Name: KPT-335
Experimental: Cohort 4 40 mg verdinexor on Days 1 and 3	Drug: Verdinexor Other Name: KPT-335
Experimental: Cohort 5 60 mg verdinexor on Days 1 and 3	Drug: Verdinexor Other Name: KPT-335
Experimental: Cohort 6 80 mg verdinexor on Days 1 and 3	Drug: Verdinexor Other Name: KPT-335
Experimental: Cohort 7 100 mg verdinexor on Days 1 and 3	Drug: Verdinexor Other Name: KPT-335

Detailed 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 subjects.

Cohorts of 8 subjects 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.

Eligibility


Ages Eligible for Study:	18 Years to 45 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Subjects must be in good health as determined by the investigator, based on the medical history, ECG, physical examination, and safety laboratory tests at screening.
Subjects 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 subject 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 subject 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 subject with active cataracts or medical history of cataracts.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02431364

Locations


Australia, Victoria
Nucleus Network
Melbourne, Victoria, Australia

Sponsors and Collaborators

Karyopharm Therapeutics Inc

Investigators


Principal Investigator:	Jason Lickliter, MD	Nucleus Network

More Information


Responsible Party:	Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier:	NCT02431364 History of Changes
Other Study ID Numbers:	KCP-335-701
Study First Received:	April 22, 2015
Last Updated:	December 2, 2015

Keywords provided by Karyopharm Therapeutics Inc:


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

ClinicalTrials.gov processed this record on July 14, 2017