Drug-Drug Interaction Study of Lorecivivint and Triamcinolone Acetonide in Healthy Volunteers

Open-Label, Parallel-Arm Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Corticosteroid Intra Articular Injection Given 7 Days Before or 7 Days After Lorecivivint Intra-articular Injection Into the Knee of Healthy Volunteers

This study will be an open-label, parallel-arm study to determine if a prior intra-articular (IA) injection of lorecivivint (LOR) affects the safety, tolerability, and/or pharmacokinetics (PK) of a subsequent IA injection of the corticosteroid triamcinolone acetonide (TA) into the same knee, and to determine if a prior IA injection of TA affects the safety or tolerability of a subsequent IA injection of LOR into the same knee.

Study Overview

• Status: Completed
• Conditions: Drug-Drug Interaction
• Intervention / Treatment: Drug: Lorecivivint (LOR); Drug: Triamcinolone acetonide (TA)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Males and females between 18 and 55 years of age, inclusive, in general good health
2. Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at Screening
3. Negative drug test for amphetamine, cocaine, methadone, opiates, phencyclidine (PCP), barbiturates, benzodiazepines, tricyclic antidepressants, and marijuana

Key Exclusion Criteria:

1. Pregnant women, breastfeeding women, and women who are not post-menopausal (defined as 12 months with no menses without an alternative medical cause) or permanently surgically sterile (includes hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) who have a positive or indeterminate pregnancy test result at the Screening Visit or Day -1
2. Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control during the study period
3. Men who are sexually active and of reproductive potential, who have partners who are capable of becoming pregnant, and who are not willing to use birth control during the study period
4. Any chronic medical condition that requires medication
5. Any history of IA injection, surgery (e.g., arthroscopy), infection, major orthopedic injury, or inflammatory rheumatic diseases (e.g., rheumatoid arthritis, gout, pseudogout) of either knee
6. Any contraindications for an IA injection in the right knee in the opinion of the Investigator
7. Previous treatment with lorecivivint (LOR)
8. Treatment with any glucocorticoids (oral, intravenous, intramuscular, IA, topical, or inhaled) within 12 weeks before Day 1
9. Consumption of grapefruit, grapefruit juice, Seville oranges, or vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts) within 10 days before Day 1
10. Known hypersensitivity to triamcinolone acetonide (TA)
11. Significant blood loss (> 500 mL) or donation of blood within 30 days of screening
12. Regular use of nicotine-containing products, including, but not limited to, cigarettes, e-cigarettes, or nicotine gum or patches
13. Any condition, that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
14. Estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2, calculated using the Modification of Diet in Renal Disease (MDRD) equation at the Screening Visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TA injection followed by LOR injection; IA injection of TA into the right knee, followed by IA injection of LOR into the same knee 7 days later.	Drug: Lorecivivint (LOR); 0.07 mg; Other Names: SM04690; Drug: Triamcinolone acetonide (TA); 40 mg
EXPERIMENTAL: LOR injection followed by TA injection; IA injection of LOR into the right knee, followed by IA injection of TA into the same knee 7 days later.	Drug: Lorecivivint (LOR); 0.07 mg; Other Names: SM04690; Drug: Triamcinolone acetonide (TA); 40 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of LOR	0, 0.25, 0.5, 1, 2, 4, 6, 8 hours after administration
AUC 0-last of LOR	0, 0.25, 0.5, 1, 2, 4, 6, 8 hours after administration
Plasma concentration profiles of LOR	0, 0.25, 0.5, 1, 2, 4, 6, 8 hours after administration
Cmax of TA	0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours after administration
AUC 0-last of TA	0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours after administration
Plasma concentration profiles of TA	0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours after administration

Collaborators and Investigators

• Sponsor: Biosplice Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 13, 2020
• Primary Completion (ACTUAL): December 22, 2020
• Study Completion (ACTUAL): December 22, 2020

Study Registration Dates

• First Submitted: October 6, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (ACTUAL): October 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 8, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: triamcinolone acetonide; lorecivivint
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; Lorecivivint
• Other Study ID Numbers: SM04690-OA-16

Drug and device information, study documents

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