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

Sponsor

Biosplice Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04598542

Collaborator

(none)

Enrollment

Location

Arms

2.3

Actual Duration (Months)

17.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Drug-Drug Interaction	Drug: Lorecivivint (LOR) Drug: Triamcinolone acetonide (TA)	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Oct 13, 2020

Actual Primary Completion Date :

Dec 22, 2020

Actual Study Completion Date :

Dec 22, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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