First-In-Human PainCart Study for STR-324

Study Overview
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Brief Summary
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This is an interventional, first-in-man study, double-blind, placebo-controlled, two-part, ascending doses study to investigate the safety, tolerability and efficacy of STR-324 infusions in healthy volunteers.

Detailed Description
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Part I : ascending doses of short lasting infusion Part II : ascending doses of long lasting infusion

Official Title
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A First-in-Human, Randomized, Double-blind, Placebo-controlled Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of STR-324 in Healthy Subjects

Conditions
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Pain

Intervention / Treatment
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* Drug: Placebo
* Drug: STR-324 Dose Level 1
* Drug: STR-324 Dose Level 2
* Drug: STR-324 Dose Level 3
* Drug: STR-324 Dose Level 4
* Drug: STR-324 Dose Level 5
* Drug: STR-324 Dose Level 6
* Drug: STR-324 Dose Level 7
* Drug: STR-324 Dose Level 8
* Drug: STR-324 Dose Level A
* Drug: STR-324 Dose Level B
* Drug: STR-324 Dose Level C
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to any study-mandated procedure Healthy male subjects, 18 to 45 years of age, inclusive at screening. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg. All males must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions. Exclusion Criteria: Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator Subject with clinically significant abnormalities in blood pressure, heart rate, ECG recording and laboratory parameters Abnormal renal function (eGFR (MDRD) < 60 mL/min/1.73m2). Previous history of seizures or epilepsy. Acute disease state (e.g. nausea, vomiting, fever, or diarrhea) within 7 days before the first study day. Positive Hepatitis B surface antigen (HBsAg), Hepatitis B antibodies, Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) Use of any medications (prescription or over-the-counter [OTC]), within 14 days of study drug administration, or less than 5 half-lives (whichever is longer). Use of any vitamin, mineral, herbal, and dietary supplements within 7 days of study drug administration, or less than 5 half-lives (whichever is longer). Participation in an investigational drug or device study within 3 months prior to first dosing. History of abuse of addictive substances or current use of substances (alcohol, illegal substances) Positive test for drugs of abuse or alcohol breath test at screening or pre-dose. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable). Loss or donation of blood over 500 mL within three months prior to screening Any current, clinically significant, known medical condition in particular any existing conditions that would affect sensitivity to cold or pain

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

Sexes Eligible for Study
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Male

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: For part I: crossover model For part II: parallel model
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I (Panel 1): STR-324 or placebo<br>Subjects will receive STR-324 dose level 1, 3, 5, 7 or placebo as a short infusion according to randomization. | Drug: Placebo<br>* Short infusion of the solution for intravenous administration, Sodium Chloride 0.9%<br>Drug: STR-324 Dose Level 1<br>* Short infusion of a solution for intravenous administration<br>Drug: STR-324 Dose Level 3<br>* Short infusion of a solution for intravenous administration<br>Drug: STR-324 Dose Level 5<br>* Short infusion of a solution for intravenous administration<br>Drug: STR-324 Dose Level 7<br>* Short infusion of a solution for intravenous administration<br>|
| Experimental: Part I (Panel 2): STR-324 or placebo<br>Subjects will receive STR-324 dose level 2, 4, 6, 8 or placebo as a short infusion according to randomization. | Drug: Placebo<br>* Short infusion of the solution for intravenous administration, Sodium Chloride 0.9%<br>Drug: STR-324 Dose Level 2<br>* Short infusion of a solution for intravenous administration<br>Drug: STR-324 Dose Level 4<br>* Short infusion of a solution for intravenous administration<br>Drug: STR-324 Dose Level 6<br>* Short infusion of a solution for intravenous administration<br>Drug: STR-324 Dose Level 8<br>* Short infusion of a solution for intravenous administration<br>|
| Experimental: Part II (Panel 1): STR-324 or placebo<br>Subjects will receive STR-324 dose level A or placebo as a long infusion according to randomization. | Drug: STR-324 Dose Level A<br>* Long infusion of a solution for intravenous administration<br>Drug: Placebo<br>* Long infusion of the solution for intravenous administration, Sodium Chloride 0.9%<br>|
| Experimental: Part II (Panel 2): STR-324 or placebo<br>Subjects will receive STR-324 dose level B or placebo as a long infusion according to randomization. | Drug: STR-324 Dose Level B<br>* Long infusion of a solution for intravenous administration<br>Drug: Placebo<br>* Long infusion of the solution for intravenous administration, Sodium Chloride 0.9%<br>|
| Experimental: Part II (Panel 3): STR-324 or placebo<br>Subjects will receive STR-324 dose level C or placebo as a long infusion according to randomization. | Drug: STR-324 Dose Level C<br>* Long infusion of a solution for intravenous administration<br>Drug: Placebo<br>* Long infusion of the solution for intravenous administration, Sodium Chloride 0.9%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: number of subjects who experience (serious) treatment emergent adverse events, potential clinically changes in vital signs, ECG, holter, physical examinations, laboratory tests and urine production |  | Day 7 (+/- 2 days) post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts I and II: Maximum plasma concentration (Cmax) |  | Up to 24 hours for Part I and up to 52 hours for Part II | 
| Parts I and II:Time to maximum plasma concentration (Tmax) |  | Up to 24 hours for Part I and up to 52 hours for Part II | 
| Parts I and II: Area under the plasma concentration-time curve from zero to infinity(AUC0-inf) |  | Up to 24 hours for Part I and up to 52 hours for Part II | 
| Parts I and II: Area under the plasma concentration-time curve from zero to the last measured concentration above the limit of quantification (AUC0-last) |  | Up to 24 hours for Part I and up to 52 hours for Part II | 
| Parts I and II: Terminal disposition rate constant (λz) with the respective half-life (t½) |  | Up to 24 hours for Part I and up to 52 hours for Part II | 
| Parts I and II: Amount excreted in urine in 24 hours |  | Up to 24 hours for Part I and up to 72 hours for Part II | 
| Parts I and II: Thermal Pain |  | Up to 5 hours for part I and up to 56 hours for part II | 
| Parts I and II: Electrical pain Stair and Burst |  | Up to 5 hours for part I and up to 56 hours for part II | 
| Parts I and II: Pressure Pain |  | Up to 5 hours for part I and up to 56 hours for part II | 
| Parts I and II: Cold Pressor |  | Up to 5 hours for part I and up to 56 hours for part II | 
| Parts I and II: Conditioned Pain Modulation Response (change from electrical stair pre- and post-cold pressor) |  | Up to 5 hours for part I and up to 56 hours for part II | 
| Parts I and II: Visual Analogue Scale Bond & Lader |  | Up to 5 hours for part I and up to 56 hours for part II | 
| Parts I and II: Visual Analogue Scale Bowdle |  | Up to 5 hours for part I and up to 56 hours for part II | 
| Part II only: Saccadic eye movement |  | Up to 56 hours | 
| Part II only: Smooth pursuit eye movement |  | Up to 56 hours | 
| Part II only: Adaptive tracking |  | Up to 56 hours | 
| Part II only: Body sway |  | Up to 56 hours | 
| Part II only: N-Back |  | Up to 56 hours | 
| Part II only: Pharmaco-EEG: power |  | Up to 56 hours | 
| Part II only: Pupillometry |  | Up to 56 hours | 
| Part II only: 49-item Addiction Center Research Inventory |  | Up to 60 hours | 
| Part II only: Bowel Function Index |  | Up to day 7 | 
| Part II - Groups 2 and 3 only: Thermal pain (Normal skin and erythema skin - UVB) |  | Up to 24 hours |