First-In-Human PainCart Study for STR-324

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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Placebo; Drug: STR-324 Dose Level 1; Drug: STR-324 Dose Level 3; Drug: STR-324 Dose Level 5; Drug: STR-324 Dose Level 7; Drug: Placebo; Drug: STR-324 Dose Level 2; Drug: STR-324 Dose Level 4; Drug: STR-324 Dose Level 6; Drug: STR-324 Dose Level 8; Drug: STR-324 Dose Level A; Drug: STR-324 Dose Level B; Drug: STR-324 Dose Level C

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • CHDR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Stragen France

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Actual): November 7, 2018
• Study Completion (Actual): November 7, 2018

Study Registration Dates

• First Submitted: January 19, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: December 11, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: STR-324-CL-039; 2014-002402-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No