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

NCT04598542 | Completed Phase 1 FDA Drug

• 1 other identifier: SM04690-OA-16
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug-Drug Interaction

Keywords

lorecivivint; triamcinolone acetonide

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (2)

TA injection followed by LOR injection

EXPERIMENTAL

IA injection of TA into the right knee, followed by IA injection of LOR into the same knee 7 days later.

Drug: Lorecivivint (LOR); Drug: Triamcinolone acetonide (TA)

LOR injection followed by TA injection

EXPERIMENTAL

IA injection of LOR into the right knee, followed by IA injection of TA into the same knee 7 days later.

Drug: Lorecivivint (LOR); Drug: Triamcinolone acetonide (TA)

Interventions

Lorecivivint (LOR) DRUG

0.07 mg

Also known as: SM04690

LOR injection followed by TA injection; TA injection followed by LOR injection

Triamcinolone acetonide (TA) DRUG

40 mg

LOR injection followed by TA injection; TA injection followed by LOR injection

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (1)

Research Site

Miami, Florida, 33126, United States

Location

Related Publications (1)

• Fineman MS, McAlindon TE, Lattermann C, Swearingen CJ, Kennedy S, Lopez VA, Simsek I, Tambiah JRS, Yazici Y. Safety, Tolerability, and Pharmacokinetics of Same-Knee Intra-Articular Injection of Corticosteroid and Lorecivivint Within 7 Days: An Open-Label, Randomized, Parallel-Arm Study. Rheumatol Ther. 2023 Dec;10(6):1741-1752. doi: 10.1007/s40744-023-00604-7. Epub 2023 Oct 30.

  PMID: 37902943 DERIVED

MeSH Terms

Interventions

lorecivivint; Triamcinolone Acetonide

Intervention Hierarchy (Ancestors)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 22, 2020
• Study Start: October 13, 2020
• Primary Completion: December 22, 2020
• Study Completion: December 22, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Locations

US (1)