Study of Safety, Tolerability, and Pharmacokinetics of Topical Selinexor (KPT-330) Diabetic Foot Ulcer (DFU) Patients

Sponsor

Karyopharm Therapeutics Inc (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02367690

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with eligible diabetic foot ulcers will be screened, treated, and followed for complete ulcer closure. This is a randomized trial. All patients will receive standard-of-care treatment. Additionally, some patients will receive treatment with topical Selinexor gel and some will receive topical placebo gel.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Foot Ulcers	Drug: Selinexor Other: Standard-of-Care Other: Vehicle Gel	Phase 1/Phase 2

Detailed Description

Approximately 30 patients who meet the eligibility criteria will be enrolled. Eligible patients with diabetic foot ulcers will be screened, randomized, treated, and followed for complete ulcer closure.

After screening, qualified patients will be treated for up to 12 weeks. Patients who achieve complete ulcer closure will be followed for an additional 12 weeks.

All patients will receive standard-of-care treatment. After randomization some patients will be treated with topical Selinexor gel twice weekly and some patients will be treated with a topical placebo gel twice weekly. Patients receiving Selinexor will be assigned to a sequential treatment cohort, either a 10 μM (μmol/L), 30 μM, or 70 μM dose.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phase 1/2, Multi-Dose, Evaluator-Blinded, Randomized, Vehicle & Standard Of Care-Controlled Dose-Escalation Study To Assess Safety, Tolerability, Pharmacokinetics Of Topical Selinexor In Patients With Diabetic Foot Ulcers

Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

May 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Cohort 1 will be randomized to one of the following treatment groups: a) Standard-of-care (SOC) + Selinexor gel, 10 μM , b) SOC + vehicle gel c) SOC alone.	Drug: Selinexor Topical gel Other Names: KPT-330 Other: Standard-of-Care Surgical debridement, sterile saline rinses, and dressing changes. Other Names: SOC Other: Vehicle Gel Topical vehicle gel with no active ingredients.
Experimental: Cohort 2 Cohort 2 will be randomized to one of the following treatment groups: Standard-of-care (SOC) + Selinexor gel, 30 μM SOC + vehicle gel SOC alone.	Drug: Selinexor Topical gel Other Names: KPT-330 Other: Standard-of-Care Surgical debridement, sterile saline rinses, and dressing changes. Other Names: SOC Other: Vehicle Gel Topical vehicle gel with no active ingredients.
Experimental: Cohort 3 Cohort 3 will be randomized to one of the following treatment groups: Standard-of-care (SOC) + Selinexor gel, 70 μM SOC + vehicle gel SOC alone.	Drug: Selinexor Topical gel Other Names: KPT-330 Other: Standard-of-Care Surgical debridement, sterile saline rinses, and dressing changes. Other Names: SOC Other: Vehicle Gel Topical vehicle gel with no active ingredients.

Arm

Intervention/Treatment

Experimental: Cohort 1

Cohort 1 will be randomized to one of the following treatment groups: a) Standard-of-care (SOC) + Selinexor gel, 10 μM , b) SOC + vehicle gel c) SOC alone.

Drug: Selinexor

Topical gel

Other Names:

KPT-330

Other: Standard-of-Care

Surgical debridement, sterile saline rinses, and dressing changes.

Other Names:

SOC

Other: Vehicle Gel

Topical vehicle gel with no active ingredients.

Experimental: Cohort 2

Cohort 2 will be randomized to one of the following treatment groups: Standard-of-care (SOC) + Selinexor gel, 30 μM SOC + vehicle gel SOC alone.

Drug: Selinexor

Topical gel

Other Names:

KPT-330

Other: Standard-of-Care

Surgical debridement, sterile saline rinses, and dressing changes.

Other Names:

SOC

Other: Vehicle Gel

Topical vehicle gel with no active ingredients.

Experimental: Cohort 3

Cohort 3 will be randomized to one of the following treatment groups: Standard-of-care (SOC) + Selinexor gel, 70 μM SOC + vehicle gel SOC alone.

Drug: Selinexor

Topical gel

Other Names:

KPT-330

Other: Standard-of-Care

Surgical debridement, sterile saline rinses, and dressing changes.

Other Names:

SOC

Other: Vehicle Gel

Topical vehicle gel with no active ingredients.

Outcome Measures

Primary Outcome Measures

Presence of Local Skin Reactions (LSR) [84 days]
Presence of local skin reactions (erythema, edema, pain, tenderness, induration, swelling, wound drainage, purulence, odor, cellulitis, callus, and maceration) within 4 cm of the diabetic foot ulcer wound edge.

Secondary Outcome Measures

Ulcer Closure [84 days]
Proportion of patients in each treatment group with complete ulcer closure of the target diabetic foot ulcer.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient has a clinical diagnosis of Type I or Type II diabetes mellitus with an HbA1c ≤ 10.0 and has a BMI ≤40.
The DFU(s) to be treated must be:
Anatomically discrete,
Non-healing, but has persisted for ≤12 months
Measures 1 cm2 ≤ area ≤ 5 cm2 following debridement,
Has a Wagner Grade 1 (i.e., not involving bone, muscle, tendons, or ligaments),
The Target DFU is located distal to the ankle (i.e., below the malleolus), and
Is able to be adequately off-loaded.
The patient has adequate arterial blood supply in the affected limb at screening.
Patient has the inability to perceive 10 grams pressure in the peri-ulcer area and other regions of the affected foot and toes using Semmes-Weinstein 5.07 monofilament at screening.

Exclusion Criteria:

Patient has a foot ulcer that is clearly of non-diabetic pathophysiology.
Patient has more than two (2) DFUs on the target lower extremity.
DFU is clinically infected.
Patient has active osteomyelitis of the foot or active, uncontrolled, connective tissue disease