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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Drug-Drug Interaction

Intervention / Treatment
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* Drug: Lorecivivint (LOR)
* Drug: Triamcinolone acetonide (TA)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males and females between 18 and 55 years of age, inclusive, in general good health Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at Screening Negative drug test for amphetamine, cocaine, methadone, opiates, phencyclidine (PCP), barbiturates, benzodiazepines, tricyclic antidepressants, and marijuana Key Exclusion Criteria: 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 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 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 Any chronic medical condition that requires medication 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 Any contraindications for an IA injection in the right knee in the opinion of the Investigator Previous treatment with lorecivivint (LOR) Treatment with any glucocorticoids (oral, intravenous, intramuscular, IA, topical, or inhaled) within 12 weeks before Day 1 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 Known hypersensitivity to triamcinolone acetonide (TA) Significant blood loss (> 500 mL) or donation of blood within 30 days of screening Regular use of nicotine-containing products, including, but not limited to, cigarettes, e-cigarettes, or nicotine gum or patches 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TA injection followed by LOR injection<br>IA injection of TA into the right knee, followed by IA injection of LOR into the same knee 7 days later. | Drug: Lorecivivint (LOR)<br>* 0.07 mg<br>* Other names: SM04690;Drug: Triamcinolone acetonide (TA)<br>* 40 mg<br>|
| Experimental: LOR injection followed by TA injection<br>IA injection of LOR into the right knee, followed by IA injection of TA into the same knee 7 days later. | Drug: Lorecivivint (LOR)<br>* 0.07 mg<br>* Other names: SM04690;Drug: Triamcinolone acetonide (TA)<br>* 40 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lorecivivint, triamcinolone acetonide