A Phase I study assessing the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of HTX-011-19 (a long acting formulation of 5% bupivacaine and 0.15% meloxicam) and HTX-011-49 (a long acting formulation of 2.5% bupivacaine and 0.075% meloxicam) after subcutaneous administration in healthy subjects.
- Conditions
- post-operative painanalgesics
- Registration Number
- NL-OMON41936
- Lead Sponsor
- Heron Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 46
1. Subject has signed the informed consent form prior to study participation.
2. Subject is a healthy male or female volunteer between 18 and 55 years old (extremes inclusive).
3. Subject has a body weight between 55 kg and 100 kg and a BMI between 18 and 30 kg/m2 (extremes inclusive).
4. Subject can stay in study center for 6 days and return to study center for 2 consecutive days thereafter, and again on Day 12 (± 2 days).
5. Subject has the ability to lie in a semi-recumbent position for at least 1.5 hours.
6. Subject is appropriate for the study in the judgment of the investigator, based on physical examination, laboratory tests, and subject*s interview.
7. Subject has a skin-type I or II (Fitzpatrick).
8. Subject is willing to use adequate contraception from the time of dosing until 90 days after the follow-up visit. o For male subjects: subjects with female partner of childbearing potential must agree to use a highly effective form of birth control, which entails the use of oral, injected or implanted hormonal methods of contraception or intra-uterine device/system by the female partner, in combination with a barrier method (e.g. condom, diaphragm, cervical cap with spermicide) during the study and for 90 days after discontinuation of treatment. Furthermore male subjects must agree not to donate sperm during participation in the trial and for 90 days after discontinuation of treatment; For female subjects: confirmed post-menopausal women, or female subjects agreeing to use a highly effective form of birth control, which entails the use of oral, injected or implanted hormonal methods of contraception or intra-uterine device/system in combination with a barrier method (e.g. condom, diaphragm, cervical cap with spermicide) during the study and for 90 days after discontinuation of treatment
1. Subject has a medical history of allergies including hypersensitivity against drug or clinically significant allergies, incl. asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
2. Subject has clinically significant abnormalities of hepatic, renal, respiratory system, endocrine system, nervous system, immune system, hematologic, psychiatric, cardiovascular system, cancer or has a history of cancer.
3. Subject has an abnormal laboratory result judged by the investigator as being clinically significant.
4. Subject has a positive urinary drug screen (incl. amphetamine, barbiturates, benzodiazepines, cocaine, marijuana, methadone, methamphetamine, morphine, phencyclidine, and tricyclic antidepressants).
5. Subject has a positive test for HIV antibody, HBsAg, or HCV antibody.
6. Subject has a QTc (Bazet) prolongation greater than or equal to 450 ms, or has significant electrocardiogram (ECG) abnormalities.
7. Subject is a heavy smoker (> 10 cigarettes or equivalents per day).
8. Subject is unwilling or unable to refrain from smoking while in the clinical research unit.
9. Subject has tattoos on the skin areas to be treated.
10. Subject has a history of hypersensitivity reactions for any IMP constituent including bupivacaine and other amide-type local anesthetics, and meloxicam.
11. Subject has a supine SBP < 90mmHg or supine SBP > 140mmHg, or supine DBP < 55mmHg or supine DBP > 90mmHg, or Pulse rate > 100 per/min.
12. Subject has used any prescription drug or herbal medicine within 14 days, OTC or vitamin supplements within 7 days prior to Day 1 of any study period.
13. Subject participated in a previous clinical trial with administered IMP within 90 days prior to Day 1 of the first study period.
14. Subject is a heavy alcohol consumer (alcohol > 23 units/week) or cannot stop drinking while in the clinical research unit.
15. Subject lost a volume of blood, including through blood donation, of more than 400 mL within 8 weeks prior to Day 1.
16. Subject is unwilling or unable to adhere to any specific protocol restriction as mentioned in Section 8.3.3 of the protocol.
17. For females: Subject is currently pregnant, breast feeding, or disagrees to avoid getting pregnant during the clinical study.
18. Subject is legally incapable or has limited legal capacity at screening.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part I<br /><br>• To assess the pharmacokinetics of bupivacaine and meloxicam after single<br /><br>ascending, subcutaneous doses of HTX-011<br /><br><br /><br>Part II<br /><br>• To assess and compare the analgesic and anesthetic effects of three<br /><br>different, single, subcutaneous doses of HTX-011<br /><br><br /><br>Part III<br /><br>• To assess the pharmacokinetics of bupivacaine and meloxicam after single<br /><br>ascending, subcutaneous doses of HTX-011-49</p><br>
- Secondary Outcome Measures
Name Time Method <p>Part I<br /><br>• To assess the safety and (local) tolerability of single ascending<br /><br>subcutaneous doses of HTX-011<br /><br>• To assess the pharmacodynamics of HTX-011 after single ascending subcutaneous<br /><br>doses of HTX-011<br /><br><br /><br>Part II<br /><br>• To compare the pharmacokinetics, safety and tolerability of three different<br /><br>single, subcutaneous doses of HTX-011<br /><br><br /><br>Part III<br /><br>• To assess the safety and (local) tolerability of single ascending<br /><br>subcutaneous doses of HTX-011-49.<br /><br>• To assess the pharmacodynamics of HTX-011-49 after single ascending<br /><br>subcutaneous doses of HTX-011-49</p><br>