A Phase I/II Clinical Pharmacology Study of ATX101 in Patients Undergoing Unilateral TKA.

JRCT ID: jRCT2051240201

Registered date:28/11/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Patients undergoing primary TKA.
• Date of first enrollment: 27/12/2024
• Target sample size: 20
• Study type: Interventional
• Intervention(s): After fixation of the knee implant prosthesis, ATX101 will be placed in the knee capsule under direct visualization.

Outcome(s)

Primary Outcome

(Pharmacokinetics Endpoints)
1) Plasma ATX101 concentrations
2) Pharmacokinetic parameters

(Safety Endpoints)
1) Adverse events
2) Clinical Laboratory tests
3) Vital Signs
4) Electrocardiograms

Secondary Outcome

(Efficacy Endpoints)
1) Area under the curve (AUC) for the Numerical Rating Scale at Rest (NRS-R) of Pain intensity
2) Time to discontinuation of opioid analgesia
3) Proportion of subjects who remain opioid free
4) Total post-surgical consumption of opioid medications
5) Total post-surgical consumption of rescue pain medications

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

1) Primary indication of TKA is pain due to osteoarthritis or post-traumatic arthritis.
2) Patients scheduled to undergo primary unilateral TKA using a cemented prosthesis, without use of surgical drain, and under bupivacaine spinal anesthesia.
3) Japanese patients, >=18 and =<85 years of age at the time of obtaining informed consent.
4) For female patients of childbearing potential, must not be pregnant or not a risk of becoming pregnant, and not breastfeeding throughout the study period.

Exclude criteria

1) Patients who have a planned concurrent surgical procedure at the time of surgery or a planned surgical procedure before the last study visit.
2) Patients who have had any previous surgery in the study knee at any time in the past or within 6 months prior to screening in the contralateral knee.
3) Patients receiving any intra-articular injection to the knee under study within 3 months prior to surgery.
4) Patients with pre-existing acute or chronic pain/restricted physical conditions.
5) Patients who is unable to discontinue use of medications or products that can impact pain control from the screening until the last study visit.
6) Patients with a BMI >=45kg/m2.
7) Patiets with significant abnormalities at screening such as left bundle-branch blocks, bifascicular blocks, second- or third-degree AV blocks, possible current ischemia, or other findings associated with significant heart disease, and those with a mean QTc >450 ms in males and >470 ms in females on ECG at screening.
8) Patients with symptomatic central nervous system (CNS) injury or disorder including epilepsy.
9) For female patients of childbearing potential, painents who intend to become pregnant or who are unwilling to use appropriate contraceptive methods from the time of obataining informed concent until 60 days after investigational product administration.
10) Patients with any clinically significant event or condition uncovered during surgery which occurs before investigational product administration, that might render the participant medically unstable or complicate the participants postsurgical course.
11) Patients who have not undergone patellar resurfacing.

Related Information

• Primary Sponsor: Nobuyo Oya