First-In-Human PainCart Study for STR-324

• ClinicalTrials.gov Identifier: NCT03430232
• Recruitment Status: Completed
• First Posted: February 12, 2018
• Last Update Posted: December 12, 2018
• Sponsor: Stragen France
• Information provided by (Responsible Party): Stragen France

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pain	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	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: For part I: crossover model For part II: parallel model
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 20, 2018
• Actual Primary Completion Date: November 7, 2018
• Actual Study Completion Date: November 7, 2018

Arms and Interventions

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
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: 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: STR-324 Dose Level A; Long infusion of a solution for intravenous administration; Drug: Placebo; Long infusion of the solution for intravenous administration, Sodium Chloride 0.9%
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: STR-324 Dose Level B; Long infusion of a solution for intravenous administration; Drug: Placebo; Long infusion of the solution for intravenous administration, Sodium Chloride 0.9%
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: STR-324 Dose Level C; Long infusion of a solution for intravenous administration; Drug: Placebo; Long infusion of the solution for intravenous administration, Sodium Chloride 0.9%

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Day 7 (+/- 2 days) post dosing ]

Secondary Outcome Measures :

1. Parts I and II: Maximum plasma concentration (Cmax) [ Time Frame: Up to 24 hours for Part I and up to 52 hours for Part II ]
2. Parts I and II:Time to maximum plasma concentration (Tmax) [ Time Frame: Up to 24 hours for Part I and up to 52 hours for Part II ]
3. Parts I and II: Area under the plasma concentration-time curve from zero to infinity(AUC0-inf) [ Time Frame: Up to 24 hours for Part I and up to 52 hours for Part II ]
4. 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) [ Time Frame: Up to 24 hours for Part I and up to 52 hours for Part II ]
5. Parts I and II: Terminal disposition rate constant (λz) with the respective half-life (t½) [ Time Frame: Up to 24 hours for Part I and up to 52 hours for Part II ]
6. Parts I and II: Amount excreted in urine in 24 hours [ Time Frame: Up to 24 hours for Part I and up to 72 hours for Part II ]
7. Parts I and II: Thermal Pain [ Time Frame: Up to 5 hours for part I and up to 56 hours for part II ]
8. Parts I and II: Electrical pain Stair and Burst [ Time Frame: Up to 5 hours for part I and up to 56 hours for part II ]
9. Parts I and II: Pressure Pain [ Time Frame: Up to 5 hours for part I and up to 56 hours for part II ]
10. Parts I and II: Cold Pressor [ Time Frame: Up to 5 hours for part I and up to 56 hours for part II ]
11. Parts I and II: Conditioned Pain Modulation Response (change from electrical stair pre- and post-cold pressor) [ Time Frame: Up to 5 hours for part I and up to 56 hours for part II ]
12. Parts I and II: Visual Analogue Scale Bond & Lader [ Time Frame: Up to 5 hours for part I and up to 56 hours for part II ]
13. Parts I and II: Visual Analogue Scale Bowdle [ Time Frame: Up to 5 hours for part I and up to 56 hours for part II ]
14. Part II only: Saccadic eye movement [ Time Frame: Up to 56 hours ]
15. Part II only: Smooth pursuit eye movement [ Time Frame: Up to 56 hours ]
16. Part II only: Adaptive tracking [ Time Frame: Up to 56 hours ]
17. Part II only: Body sway [ Time Frame: Up to 56 hours ]
18. Part II only: N-Back [ Time Frame: Up to 56 hours ]
19. Part II only: Pharmaco-EEG: power [ Time Frame: Up to 56 hours ]
20. Part II only: Pupillometry [ Time Frame: Up to 56 hours ]
21. Part II only: 49-item Addiction Center Research Inventory [ Time Frame: Up to 60 hours ]
22. Part II only: Bowel Function Index [ Time Frame: Up to day 7 ]
23. Part II - Groups 2 and 3 only: Thermal pain (Normal skin and erythema skin - UVB) [ Time Frame: Up to 24 hours ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Netherlands

CHDR

Leiden, Netherlands, 2333

Sponsors and Collaborators

Stragen France

More Information

• Responsible Party: Stragen France
• ClinicalTrials.gov Identifier: NCT03430232
• Other Study ID Numbers: STR-324-CL-039; 2014-002402-21 ( EudraCT Number )
• First Posted: February 12, 2018
• Last Update Posted: December 12, 2018
• Last Verified: December 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No