Multiple Ascending Dose Safety Study of ShK-186 (Dalazatide) in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to examine safety outcomes in healthy volunteers after systemic administration of multiple ascending doses of dalazatide.

Detailed Description
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The purpose of this study is to examine safety outcomes in healthy volunteers after systemic administration of multiple ascending doses of dalazatide delivered via subcutaneous injection twice per week for a total of 9 doses.

Official Title
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A Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of ShK-186

Conditions
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Healthy

Intervention / Treatment
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* Drug: dalazatide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy normal male and female subjects, ages 18 to 45, inclusive; able to communicate and able to provide valid, written informed consent; within the body mass index (BMI) range of approximately 18.0 to 30.0 kg/m2, inclusive; minimum weight of 50 kg; willingness to remain totally abstinent or use adequate contraception; e.g., 2 of the following methods: hormonal contraceptive, intrauterine device, condom, diaphragm, and spermicidal gel/foam) in order to prevent pregnancy from the screening visit until 60 days after the follow-up visit. For men, the donation of sperm during this period is also prohibited. Exclusion Criteria: the presence of clinically significant medical history as determined by the investigator. the history of clinically significant cardiac abnormalities or presence of clinically significant abnormality on 12-lead ECG. the history of pre-existing paresthesia or neuropathy; abnormalities on neurologic exam at screening or baseline the history of any cancer requiring systemic chemotherapy or radiation; individuals with a history of non-melanoma skin cancer, nonrecurring carcinoma in situ treated with laser or cryotherapy or cervical cancer-in-situ, resected surgically with no evidence of disease, may be accepted on a case by case basis at the discretion of the Investigator; the presence of acute infection or history of acute infection within 7 days prior to receipt of the study drug; additionally, oral temperature may not exceed 37.4°C at baseline; the presence of clinically significant laboratory abnormalities (chemistry panel of 20 analytes [Chem-20; fasted 10-12 hours], complete blood count [CBC], and urinalysis [UA]) as determined by the investigator; positive urine drug screen for drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, cotinine, tricyclic antidepressants and alcohol) at Screening or at Baseline. typical intake of more than 7 units of alcohol per week (one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits) a positive hepatitis screen (Hepatitis BsAg or anti-HCV) or positive Human Immunodeficiency Virus (HIV) antibody test ; a history of multiple drug allergies that are important in the view of the Investigator; any history of anaphylaxis or a history of allergy to a medication, diet, or environmental exposure (including bee stings) that are important in the view of the Investigator; participation in another clinical trial with receipt of an investigational product within 60 days of dose administration (or 5 half lives, whichever is longer); recent (within 1 year of Screening) history of illicit drug use; history of alcohol abuse that is important in the view of the Investigator inadequate venous access that would interfere with obtaining blood samples; use of prescription medications, over the counter products, herbal remedies and nutritional supplements within 7 days of study drug administration and throughout the study, or the anticipated need for prescription medications prior to Study Completion; recipients of blood transfusion or transfusion of blood or plasma products within 60 days of study drug administration; donation of blood > 500 mL within 2 months of study drug administration; positive pregnancy test at screening or at baseline (female subjects only); history within the past 3 months of eating disorders or other conditions which may lead to suspicion about the participant's nutritional status; inability or unwillingness to comply with study restrictions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dalazatide 5ug<br>8 subjects, 6 given active agent and 2 given placebo | Drug: dalazatide<br>* Different doses of drug, subcutaneous injection twice per week for a total of 9 doses.<br>* Other names: ShK-186;Drug: placebo<br>* Placebo delivered via subcutaneous administration twice per week for a total of 9 doses<br>* Other names: Sub Q Placebo;|
| Experimental: dalazatide 15ug<br>8 subjects, 6 given active agent and 2 given placebo | Drug: dalazatide<br>* Different doses of drug, subcutaneous injection twice per week for a total of 9 doses.<br>* Other names: ShK-186;Drug: placebo<br>* Placebo delivered via subcutaneous administration twice per week for a total of 9 doses<br>* Other names: Sub Q Placebo;|
| Experimental: dalazatide 30ug<br>8 subjects, 6 given active agent and 2 given placebo | Drug: dalazatide<br>* Different doses of drug, subcutaneous injection twice per week for a total of 9 doses.<br>* Other names: ShK-186;Drug: placebo<br>* Placebo delivered via subcutaneous administration twice per week for a total of 9 doses<br>* Other names: Sub Q Placebo;|
| Experimental: dalazatide 60ug<br>8 subjects, 6 given active agent and 2 given placebo | Drug: dalazatide<br>* Different doses of drug, subcutaneous injection twice per week for a total of 9 doses.<br>* Other names: ShK-186;Drug: placebo<br>* Placebo delivered via subcutaneous administration twice per week for a total of 9 doses<br>* Other names: Sub Q Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects with adverse events |  | From randomization to Day 57 (14 time points) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects with changes in vital signs | Vital signs include temperature, respiratory rate, supine blood pressure and pulse. | From randomization through Day 57 (14 time points) | 
| Subjects with changes in symptom-directed physical examinations |  | From date of randomization to day 57 (14 timepoints) | 
| Subjects with changes in 12-lead electrocardiograms |  | From date of randomization to day 57 (5 timepoints) | 
| PK parameters | Parameters include Area under the plasma concentration versus time curve of dalazatide (AUC) | pre-dose, 15 minutes post dose, 30 minutes post dose, 1 hour post dose, 2 hours post dose, 4 hours post dose, 8 hours post dose, 12 hours post dose | 
| Presence of specific anti-drug antibody | Serum evaluated for specific anti-drug antibody using ELISA-based immunoassay. | From date of randomization through Day 57 (4 timepoints). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ShK-186, dalazatide, Kv1.3, SHK