Sofusa System With Sumatriptan (KC5010) Phase 1 Dose Escalation Safety and PK Study (KCC-SMT-002)

Study Overview
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Brief Summary
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Study KCC-SMT-002, is a Phase 1, single-site, open-label, non-randomized, crossover, flexible dose design study to investigate the pharmacokinetic (PK) and safety comparing the Sofusa™ system with sumatriptan (KC5010) to Imitrex® oral tablets in 17 healthy volunteers.

Official Title
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An Open-Label Phase 1 Study to Establish the Pharmacokinetics and Safety of Sumatriptan Succinate Administered Via the Sofusa™ DoseConnect™ System at Escalating Doses Compared to Oral Imitrex® Single 100 mg Dose in Healthy Subjects

Conditions
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Migraine Disorders

Intervention / Treatment
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* Drug: Sumatriptan Succinate Oral Tablet
* Combination Product: Transdermal delivery of sumatriptan succinate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give voluntary written informed consent (personally signed and dated) and HIPPA Authorization prior to any study related procedures. Available to participate for the entire study period. Be a male or female person between 18 and 55 years (inclusive) of age. Healthy as determined by the investigator based on a medical evaluation including history, physical examination, electrocardiogram (ECG), and laboratory tests. Have systolic blood pressure (sitting) of < 140 mmHg and diastolic blood pressure of < 90 mmHg after 5 minutes of rest. Minor excursions in blood pressure outside of this range may be acceptable if determined not to be clinically significant by the study physician or medical monitor. Have resting pulse rate (sitting) within normal range of 60-100 bpm. Minor excursions in resting pulse outside of this range may be acceptable if determined not to be clinically significant by the study physician or the medical monitor. Females must be either postmenopausal for at least 1 year, surgically sterile (bilateral oophorectomy, tubal ligation, tubal occlusion, hysterectomy), or using adequate contraception from screening until 90 days after completion of study participation. Adequate contraception is defined as true abstinence, a vasectomized partner, or one of the following in combination with a diaphragm, cervical cap, or a condom: Hormonal contraceptives (oral, implant, patch, injection) Intrauterine device Males must use adequate contraception and must not donate sperm from first admission to the clinical research center until 90 days after completion of study participation. Adequate contraception is defined as true abstinence, vasectomy, a partner who is surgically sterile (bilateral oophorectomy, tubal ligation, tubal occlusion, hysterectomy), or one of the following in combination with a diaphragm, cervical cap, or a condom: Hormonal contraceptives (oral, implant, patch, injection) Intrauterine device Have a body weight above 50 kg and below 90 kg (inclusive). Be able to communicate effectively with the study personnel and understand and comply with all study requirements. Exclusion criteria: Women who are pregnant or lactating. Current use or has used tobacco- or nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, etc.) 30 days prior to investigational product administration. A cotinine test (with a cut-off of 200 mg) will be performed at screening and admission to the study center. Recent history (i.e. within 2 years) of alcohol abuse, illicit drug use, or significant mental illness. Positive screen for substances of abuse. A positive screening result for human immunodeficiency virus (HIV) antibody, Hepatitis B surface antigen (HBsAg), or Hepatitis C antibody (anti-HCV). Any disease or condition (medical or surgical) that might compromise a major body system (e.g. cardiovascular, respiratory, etc.) or conditions that may interfere with the absorption, distribution, metabolism, or excretion of the study medication. Any bleeding disorders or use of anticoagulants. Any conditions (e.g. diabetes, edema, scleroderma) or receiving medications (e.g. steroids, antibiotics) that alter skin integrity and/or healing. Any known condition or receiving medications causing hypo/hyperpigmentation or photosensitivity. Presence or history of hypertension or other cardiovascular abnormalities such as, but not limited to, myocardial infarction, heart failure, arrhythmia, stroke, or peripheral vascular disease or any other cardiovascular disease that requires the subject to wear a pacemaker. Use of a drug therapy known to induce or inhibit hepatic drug metabolism within 30 days prior to the Treatment visit for dosing. Patient has received a live attenuated vaccine within the 4 weeks prior to treatment or plans to receive one during the study. Febrile illness within 7 days of Treatment visit for dosing. Has a positive history or known sensitivity to sumatriptan or other triptans. Any history of sensitivity to methylene blue, fluorescein or calcein, or other similar dye product. Subjects who have used ergotamine-containing or ergot-type medications (like dihydrogergotamine or methysergide) within the past week. The Imitrex® label specifies that these medication are contraindicated within 24 hours of use. Diagnosed with ischemic bowel disease or severe hepatic impairment which are known contraindications to sumatriptan. Concomitant therapy with the following medications which have significant drug interactions with sumatriptan: selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitor (SNRIs), tricyclic antidepressants, and monomine oxidase (MAO) inhibitors due to an increased risk of serotonin syndrome. Subjects receiving these medications may enroll in the study if these medications have been discontinued for 5 or more half-lives prior to the first Treatment visit. Subjects who are currently taking prescription or over-the-counter medications (including vitamins and herbal preparations) that could interfere with the evaluation or the safety of the subject, as determined by the Investigator. Participation in the treatment phase of a clinical study or receipt of an investigational drug or medical device within 30 days prior to the Treatment visit for dosing. History of difficulty with phlebotomy procedures. Donated blood (>400 mL) or blood products within 45 days prior to the Treatment visit for dosing. Subjects who have skin conditions or tattoos extensive enough to cover areas where the device is to be applied. Any history of skin contact sensitivity to metals, plastics or adhesives. Has a condition that, in the opinion of the Investigator, may increase the risk to the subject and/or the interpretation of the data.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sumatriptan Succinate Oral Tablet<br>100 mg oral tablet commercial Imitrex sumatriptan succinate tablet | Drug: Sumatriptan Succinate Oral Tablet<br>* Sumatriptan succinate commercial Imitrex 100 mg tablet<br>|
| Experimental: Sofusa Profile #1<br>Combination device for transdermal delivery of sumatriptan succinate Current approved dose (SC) | Combination Product: Transdermal delivery of sumatriptan succinate<br>* Sumatriptan succinate transdermal drug delivery system<br>* Other names: KC5010;|
| Experimental: Sofusa Dose Profile #2<br>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #1 | Combination Product: Transdermal delivery of sumatriptan succinate<br>* Sumatriptan succinate transdermal drug delivery system<br>* Other names: KC5010;|
| Experimental: Sofusa Dose Profile #3<br>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #2 | Combination Product: Transdermal delivery of sumatriptan succinate<br>* Sumatriptan succinate transdermal drug delivery system<br>* Other names: KC5010;|
| Experimental: Sofusa Dose Profile #4<br>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from Sofusa Dose Profile #3 | Combination Product: Transdermal delivery of sumatriptan succinate<br>* Sumatriptan succinate transdermal drug delivery system<br>* Other names: KC5010;|
| Experimental: Sofusa Dose Profile #5<br>Combination device for transdermal delivery of sumatriptan succinate- adjust dose and flow rate to achieve PK profile based on results from prior Sofusa Dose Profile #2-4 | Combination Product: Transdermal delivery of sumatriptan succinate<br>* Sumatriptan succinate transdermal drug delivery system<br>* Other names: KC5010;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Cmax | Pharmacokinetic profile with Cmax (maximum concentration) of drug in blood, ng/mL | 48 hours after dosing begins | 
| PK AUC | Pharmacokinetic profile AUC (area under the curve) of drug in blood, ng-hr/mL | 48 hours after dosing begins | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermatological skin response (Draize scale) | Skin response as measured on modified Draize scale (erythema, edema, etc.) | From Predose to 168 hours after device application | 
| Pain of application and wear (VAS scale) | Pain as reported on Visual Analog Scale | Upon application and after wear |