A Phase 2, Randomized, Pilot Study to Investigate the Safety, Efficacy, Pharmacokinetics and Bioavailability of HTX-011, HTX-002, or HTX-009 Administered Via Injection and/or Topical Application Following Unilateral Open Inguinal Herniorrhaphy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 463
- 试验地点
- 3
- 主要终点
- Mean Summed Pain Intensity (SPI) Score
研究概览
简要总结
A Phase 2, Randomized, Pilot Study to Investigate the Safety, Efficacy, Pharmacokinetics and Bioavailability of HTX-011, HTX-002, or HTX-009 Administered Via Injection and/or Topical Application Following Unilateral Open Inguinal Herniorrhaphy
详细描述
This study includes multiple formulations for formulation selection of the fixed-combination product and for the factorial design assessment of the contribution of each component. HTX-011 is the initial formulation studied (HTX-011-19). HTX-011A is the second formulation studied (HTX-011-49). HTX-011B is the final formulation studied (HTX-011-56), which was also included in subsequent Phase 2b and Phase 3 studies. For the factorial design assessment, HTX-002, a bupivacaine-only formulation in the same HTX-011 proprietary polymer, and HTX-009, a meloxicam-only formulation in the same HTX-011 proprietary polymer, were evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be male or female 18 years of age or older.
- •Female subjects are eligible only if all of the following apply:
- •Not pregnant (female subject of child bearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test before surgery)
- •Not lactating
- •Not planning to become pregnant during the study
- •Be surgically sterile; or at least two years post-menopausal; or have a monogamous partner who is surgically sterile; or is practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening visits and commits to the use of an acceptable form of birth control for the duration of the study and for 30 days from completion of the study
- •o Must be surgically sterile (biologically or surgically) or commit to the use of a reliable method of birth control for the duration of the study until at least 1 week after the administration of study medication.
- •Plan to undergo a unilateral inguinal herniorrhaphy
- •Have the ability and be willing to comply with the study procedures
- •Must be able to understand study procedures and give informed consent for the conduct for all study procedures, using an IRB approved consent form.
排除标准
- •Unwilling to sign informed consent or not willing or able to complete all study procedures
- •Have a contraindication or be allergic to any medication to be used during the trial period
- •Have clinically significant cardiac abnormalities, that in the opinion of the investigator would pose a health risk to the subject should they participate in the trial
- •Have American Society of Anesthesiologists (ASA) Physical Status classification system category 4 or greater (Appendix E)
- •Have clinically significant renal or hepatic abnormalities (defined as an AST or ALT > 3x ULN, creatinine > 2x ULN)
- •Have another painful condition that may confound pain assessments
- •Have another surgery planned within 30 days of procedure, or presents with bilateral or recurrent inguinal hernia, other hernia presentations, or hernias with large scrotal component that would be difficult to reduce surgically
- •Have a known or suspected history of alcohol or drug abuse, or a positive drug screen
- •Currently taking analgesics for a chronically painful condition, or has taken long acting opioids within 3 days of surgery, or taken any opioids within 24 hours of surgery
- •Subjects with documented sleep apnea or are on home continuous positive airway pressure (CPAP)
- •Female subjects who are pregnant (positive pregnancy test at screening or on the day of surgery)
- •Subjects who are receiving oxygen therapy at the time of screening
- •Have participated in a clinical trial within 30 days of planned surgery
- •Have a body mass index (BMI) > 39 kg/m2
研究组 & 干预措施
Part A, Cohort C
HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg by instillation.
干预措施: HTX-011 (Drug)
Part F, Cohort A
HTX-011B (bupivacaine/meloxicam), 300 mg/9 mg by instillation.
干预措施: HTX-011B (Drug)
Part A, Cohort A
HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg by injection.
干预措施: HTX-011 (Drug)
Part A, Cohort B
HTX-011(bupivacaine/meloxicam), 400 mg/12 mg by injection.
干预措施: HTX-011 (Drug)
Part A, Cohort D
HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg by instillation.
干预措施: HTX-011 (Drug)
Part A, Cohort E
HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg by injection and instillation (combination).
干预措施: HTX-011 (Drug)
Part A, Cohort F
Saline placebo by injection.
干预措施: Placebo (Drug)
Part B, Cohort A
HTX-011A (bupivacaine/meloxicam), 200 mg/6 mg by injection.
干预措施: HTX-011A (Drug)
Part B, Cohort B
HTX-011A (bupivacaine/meloxicam) 400 mg12 mg by injection.
干预措施: HTX-011A (Drug)
Part B, Cohort C
HTX-011B (bupivacaine/meloxicam), 200 mg/6 mg by injection.
干预措施: HTX-011B (Drug)
Part B, Cohort D
HTX-011B (bupivacaine/meloxicam), 400 mg/12 mg by injection.
干预措施: HTX-011B (Drug)
Part B, Cohort E
Saline placebo by injection.
干预措施: Placebo (Drug)
Part C, Cohort A
HTX-002, 200 mg by injection or instillation.
干预措施: HTX-002 (Drug)
Part B, Cohort F
HTX-002, 400 mg by injection or instillation.
干预措施: HTX-002 (Drug)
Part C, Cohort B
HTX-011B (bupivacaine/meloxicam), 200 mg/6 mg by instillation.
干预措施: HTX-011B (Drug)
Part B, Cohort G
HTX-011B (bupivacaine/meloxicam), 400 mg/12 mg by instillation.
干预措施: HTX-011B (Drug)
Part C, Cohort C
Saline placebo by instillation.
干预措施: Placebo (Drug)
Part C, Cohort D
Bupivacaine HCI (Marcaine), 75 mg by injection.
干预措施: Bupivacaine HCI (Marcaine) (Drug)
Part D, Cohort A
HTX-011B (bupivacaine/meloxicam), 400 mg/13 mg via a combination of injection and instillation.
干预措施: HTX-011B (Drug)
Part E, Cohort A
HTX-009, 12 mg by injection and instillation (combination).
干预措施: HTX-009 (Drug)
Part F, Cohort B
Bupivacaine HCI (Marcaine), 75 mg by injection.
干预措施: Bupivacaine HCI (Marcaine) (Drug)
Part F, Cohort C
Saline placebo by injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Summed Pain Intensity (SPI) Score
时间窗: 24 hours
Subjects assessed pain intensity for their current pain with the 11-point (0 to 10) Numeric Rating Scale NRS where "0" equated to "no pain" and "10" equated to "the worst pain imaginable". Pain intensity was assessed at rest (NRS-R) after the subject had been supine for a minimum of 5 minutes and with activity (NRS-A) sitting up from a supine position. The SPI is derived by summing the pain intensity score weighted by the scheduled time duration. SPI0-24 was calculated by summing the Pain intensity (PI) score at the relevant time points weighted by the scheduled time duration since the prior PI assessment as follows: SPI0-24= PI1+PI2+2\*PI4+2\*PI6+2\*PI8+2\*PI10+2\*PI12+2\*PI14+4\*PI18+6\*PI24. Min = 0 (if PI=0 at every time) and Max = 240 (if PI=10 at every time).
次要结局
未报告次要终点