Relative Bioavailability Study of MELT-100, IV Midazolam, and IV Ketamine

A Pivotal Phase 1, Randomized, Single-Dose, 4-Period, Crossover Relative Bioavailability Study of MELT-100, IV Midazolam, and IV Ketamine Under Fasted Conditions in Healthy Volunteers

A Pivotal Phase 1, Randomized, Single-Dose, 4-Period, Crossover Relative Bioavailability Study of MELT-100, IV Midazolam, and IV Ketamine under Fasted Conditions in Healthy Volunteers

Study Overview

• Status: Completed
• Conditions: Procedural Sedation
• Intervention / Treatment: Drug: midazolam / ketamine sublingual tablet

Detailed Description

A Pivotal Phase 1, Randomized, Single-Dose, 4-Period, Crossover Relative Bioavailability Study of 2 doses of 3.5mgMELT-100, IV Midazolam, and IV Ketamine 18mg under Fasted Conditions in Healthy Volunteers

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Able to understand and voluntarily consent to participation in this study and provides written informed consent before the start of any study-specific procedures.

  2. Healthy adult male or female at least 55 years of age. 3. Negative test for SARS-CoV2 (COVID-19) 4. Normally active and otherwise judged to be in good health on the basis of medical history and physical examination.

  5. Has vital signs (measured sitting after a minimum 3 minutes of rest) at Screening within the following ranges: heart rate: 40 to 100 bpm; systolic blood pressure (BP): 90 to145 mmHg; diastolic BP: 50 to 95 mmHg. Out-of-range vital signs may be repeated once.

  6. Has a body temperature ≤37.7 degrees C 7. Body weight at least 55 kg 8. Body mass index (BMI) 18.0 to 32.0 kg/m2 (inclusive) 9. Female subjects are eligible only if the following applies: Surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy), or postmenopausal (confirmed with serum FSH at Screening) 10. Male subjects must either be surgically sterile (vasectomy at least 3 months prior to first dose) or agree to use an acceptable method of birth control (see Section 4.4) from Screening through EOS.

  11. Is willing and able to remain in the study unit for the entire duration of each confinement period.

Exclusion Criteria:

• 1. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, ophthalmologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.

  2. Has a history of glaucoma, asthma, chronic obstructive pulmonary disease, or thyroid disease.

  3. History and/or family history of congenital long QT syndrome, unexplained syncope, or other additional risks for Torsade de Pointes, or sudden premature death.

  4. Clinically significant illnesses within 4 weeks of the administration of study medication (including flu, flu-like symptoms, diarrhea, vomiting, fever, sore throat) or acute illness at the time of either the pre-study medical evaluation or dosing.

  5. Has been in contact with someone within the last month who has tested positive for SARS-CoV-2.

  6. History of COVID-19. 7. Clinically significant surgery within 4 weeks prior to the administration of the study medication.

  8. Has participated in another clinical trial (randomized subjects only) within 30 days before the first dose of study medication.

  9. An active malignancy of any type or has been diagnosed with cancer within 5 years prior to Screening (excluding squamous or basal cell carcinoma of the skin).

  10. History or presence of allergic or adverse response to midazolam, ketamine, 11. Use of any over-the-counter (OTC) medication (including nutritional or dietary supplements, herbal preparations, or vitamins) within 14 days before the first dose of study medication until the EOS without evaluation and approval by the Investigator.

  12. Use of any prescription medication, except statin drugs or hormonal replacement therapy, from 14 days before the first dose of study medication until the EOS without evaluation and approval by the Investigator.

  13. Have had a depot injection or an implant of any drugs 3 months prior to administration of study medication.

  14. Has been treated with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) enzymes (e.g., barbiturates, phenothiazines, cimetidine, carbamazepine) within 30 days before the first dose of study medication, and that, in the Investigators judgment, may impact subject safety or the validity of the study results.

Specifically, the use of any drugs known to inhibit CYP2C9 and CYP3A4 enzymes (for example, amiodarone, fluconazole, ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin) or any drugs that are highly protein-bound (for example, warfarin, cyclosporine, amphotericin B) within 30 days prior to the first dose of study medication, and that in the Investigator's judgment may impact subject safety or the validity of the study results.

15. Blood or plasma donation within 30 days before the first dose of study medication until the EOS. It is recommended that blood/plasma donations not be made for at least 30 days after the EOS.

16. Has any prior history of substance abuse or treatment (including alcohol).

1. History of significant alcohol abuse within 6 months of Screening or any indication of the regular use of more than 2 units of alcohol per day

   (1 unit = 50 mL of wine or 360 mL of beer or 45 mL of alcohol 40%).

2. History of use of marijuana within 3 months of Screening or drugs such as cocaine, phencyclidine (PCP), within 1 year of Screening.

   17. Smoking or use of tobacco- or nicotine-containing products within 60 days before the first dose of study medication until the EOS Note: Nonsmokers are preferred for this study. 18. Any food allergy, intolerance, restriction, or special diet that, in the opinion of the Investigator, contraindicates the subjects participation in this study.

   19. Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.

   20. Consumption of beverages or foods that contain alcohol, poppy seeds, broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine from 48 hours before the first dose of study medication until the EOS.

   Subject must not consume grapefruit, orange, or apple juice from 7 days before the first dose of study medication until the EOS.

   Subjects will be instructed not to consume any of the above products; however, allowance for an isolated single incidental consumption may be evaluated and approved by the study Investigator based on the potential for interaction with the study drug.

   21. Engagement in strenuous exercise from 48 hours before the first dose of study medication until the EOS.

   22. A clinically significant abnormal finding on the physical examination, medical history, or clinical laboratory results at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MELT-100 3/25; MELT-100 3mg midazolam / 25 mg ketamine	Drug: midazolam / ketamine sublingual tablet; sublingual tablet
Active Comparator: MELT-100 2 x 3/25; MELT-100 2 doses of 3mg midazolam / 25mg ketamine	Drug: midazolam / ketamine sublingual tablet; sublingual tablet
Active Comparator: ketamine IV 18mg	Drug: midazolam / ketamine sublingual tablet; sublingual tablet
Active Comparator: Midazolam IV 3.5mg	Drug: midazolam / ketamine sublingual tablet; sublingual tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum Concentration	24 hours
AUClast	Area under the curve	24 hours

Collaborators and Investigators

• Sponsor: Melt Pharmaceuticals
• Collaborators: Worldwide Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): January 14, 2021

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: MELT-100-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No