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

NCT04767035 | Completed Phase 1 FDA Drug

• 1 other identifier: MELT-100-002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Procedural Sedation

Outcome Measures

Primary Outcomes (2)

• Cmax

  Maximum Concentration

  24 hours

• AUClast

  Area under the curve

  24 hours

Study Arms (4)

MELT-100 3/25

ACTIVE COMPARATOR

MELT-100 3mg midazolam / 25 mg ketamine

Drug: midazolam / ketamine sublingual tablet

MELT-100 2 x 3/25

ACTIVE COMPARATOR

MELT-100 2 doses of 3mg midazolam / 25mg ketamine

Drug: midazolam / ketamine sublingual tablet

ketamine IV 18mg

ACTIVE COMPARATOR

Drug: midazolam / ketamine sublingual tablet

Midazolam IV 3.5mg

ACTIVE COMPARATOR

Drug: midazolam / ketamine sublingual tablet

Interventions

midazolam / ketamine sublingual tablet DRUG

sublingual tablet

MELT-100 2 x 3/25; MELT-100 3/25; Midazolam IV 3.5mg; ketamine IV 18mg

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Able to understand and voluntarily consent to participation in this study and provides written informed consent before the start of any study-specific procedures.
• \. 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.
• \. 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.
• \. 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.
• \. Is willing and able to remain in the study unit for the entire duration of each confinement period.

You may not qualify if:

• \. 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.
• \. Has a history of glaucoma, asthma, chronic obstructive pulmonary disease, or thyroid disease.
• \. History and/or family history of congenital long QT syndrome, unexplained syncope, or other additional risks for Torsade de Pointes, or sudden premature death.
• \. 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.
• \. Has been in contact with someone within the last month who has tested positive for SARS-CoV-2.
• \. History of COVID-19. 7. Clinically significant surgery within 4 weeks prior to the administration of the study medication.
• \. Has participated in another clinical trial (randomized subjects only) within 30 days before the first dose of study medication.
• \. 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).
• \. 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.
• \. 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.
• \. Have had a depot injection or an implant of any drugs 3 months prior to administration of study medication.
• \. 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.
• \. 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.
• \. Has any prior history of substance abuse or treatment (including alcohol).

Sponsors & Collaborators

• Melt Pharmaceuticals: lead
• Worldwide Clinical Trials: collaborator

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 4-period 4-arm crossover relative bioavailability

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: February 23, 2021
• Study Start: December 1, 2020
• Primary Completion: January 14, 2021
• Study Completion: January 14, 2021
• Last Updated: February 23, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)