<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04485702</url>
  </required_header>
  <id_info>
    <org_study_id>MELT-100-001</org_study_id>
    <nct_id>NCT04485702</nct_id>
  </id_info>
  <brief_title>Phase 1 Bioavailability Study of MELT-100 (Midazolam and Ketamine Sublingual) and IV Midazolam or Ketamine</brief_title>
  <official_title>A Pilot Phase 1, Randomized, Single-Dose, 6-Sequences, 3-Period, Crossover Bioavailability Study of MELT-100 (Midazolam and Ketamine Sublingual Tablet) and Intravenous Midazolam or Ketamine in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Melt Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Worldwide Clinical Trials</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Melt Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Comparative Bioavailability study testing MELT-100 (midazolam and ketamine sublingual tablet)&#xD;
      and IV midazolam or ketamine in healthy volunteers&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Actual">August 29, 2020</completion_date>
  <primary_completion_date type="Actual">August 29, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Randomized, Single-Dose, 6-Sequence, 3-Period, Crossover</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>randomization</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Peak Plasma Concentration (Cmax)</measure>
    <time_frame>24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to peak plasma concentration (Tmax)</measure>
    <time_frame>24 hours</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>MELT-100</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3mg midazolam and 25mg ketamine sublingual tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IV midazolam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2mg Intravenous midazolam</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IV ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>6mg Intravenous ketamine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam injection</intervention_name>
    <description>2mg IV</description>
    <arm_group_label>IV midazolam</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine Injectable Product</intervention_name>
    <description>6mg IV</description>
    <arm_group_label>IV ketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MELT-100</intervention_name>
    <description>midazolam 3mg and ketamine 25mg SL tablet</description>
    <arm_group_label>MELT-100</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A subject must satisfy all of the following criteria to be eligible for study&#xD;
             participation:&#xD;
&#xD;
               1. Able to understand and voluntarily consent to participation in this study, and&#xD;
                  provides written informed consent before the start of any study-specific&#xD;
                  procedures.&#xD;
&#xD;
               2. Healthy adult male or female ≥55 years of age.&#xD;
&#xD;
               3. Normally active and otherwise judged to be in good health on the basis of medical&#xD;
                  history and physical examination.&#xD;
&#xD;
               4. Has vital signs (measured sitting after a minimum 3 minutes rest) at Screening&#xD;
                  within the following ranges: heart rate: 40-100 bpm; systolic blood pressure&#xD;
                  (BP): 90-145 mmHg; diastolic BP: 50-95 mmHg. Out-of-range vital signs may be&#xD;
                  repeated once.&#xD;
&#xD;
               5. Has a body temperature ≤37.7 degrees C&#xD;
&#xD;
               6. Body weight ≥55 kg&#xD;
&#xD;
               7. Body mass index (BMI) 18.0 to 32.0 kg/m2 (inclusive)&#xD;
&#xD;
               8. Female subjects are eligible only if the following applies:&#xD;
&#xD;
                  Surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral&#xD;
                  oophorectomy), or postmenopausal (confirmed with serum FSH at Screening)&#xD;
&#xD;
               9. Male subjects must either be surgically sterile (vasectomy at least 3 months&#xD;
                  prior to first dose) or agree to use an acceptable method of birth control (see&#xD;
                  Section 4.4) from Screening through EOS.&#xD;
&#xD;
              10. Is willing and able to remain in the study unit for the entire duration of each&#xD;
                  confinement period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects will be excluded from study participation for any of the following:&#xD;
&#xD;
               1. History or presence of clinically significant cardiovascular, pulmonary, hepatic,&#xD;
                  renal, hematologic, gastrointestinal, endocrine, immunologic, ophthalmologic,&#xD;
                  dermatologic, neurologic, oncologic, or psychiatric disease or any other&#xD;
                  condition that, in the opinion of the Investigator, would jeopardize the safety&#xD;
                  of the subject or the validity of the study results.&#xD;
&#xD;
               2. Has a history of glaucoma, asthma, chronic obstructive pulmonary disease, or&#xD;
                  thyroid disease.&#xD;
&#xD;
               3. Clinically significant illnesses within 4 weeks of the administration of study&#xD;
                  medication (including flu, flu-like symptoms, diarrhea, vomiting, fever, sore&#xD;
                  throat) or acute illness at the time of either the pre-study medical evaluation&#xD;
                  or dosing.&#xD;
&#xD;
               4. Has been in contact with someone within the last month who has tested positive&#xD;
                  for SARS-CoV-2.&#xD;
&#xD;
               5. Clinically significant surgery within 4 weeks prior to the administration of the&#xD;
                  study medication.&#xD;
&#xD;
               6. Has participated in another clinical trial (randomized subjects only) within 30&#xD;
                  days before the first dose of study medication.&#xD;
&#xD;
               7. An active malignancy of any type, or has been diagnosed with cancer within 5&#xD;
                  years prior to Screening (excluding squamous or basal cell carcinoma of the&#xD;
                  skin).&#xD;
&#xD;
               8. History or presence of allergic or adverse response to midazolam, ketamine,&#xD;
                  Versed, KETALAR, or any ingredients of MELT-100 or related drugs.&#xD;
&#xD;
               9. Use of any over-the-counter (OTC) medication (including nutritional or dietary&#xD;
                  supplements, herbal preparations, or vitamins) within 7 days before the first&#xD;
                  dose of study medication until the EOS without evaluation and approval by the&#xD;
                  Investigator.&#xD;
&#xD;
              10. Use of any prescription medication, except statin drugs or hormonal replacement&#xD;
                  therapy, from 14 days before the first dose of study medication until the EOS&#xD;
                  without evaluation and approval by the Investigator.&#xD;
&#xD;
              11. Have had a depot injection or an implant of any drugs 3 months prior to&#xD;
                  administration of study medication.&#xD;
&#xD;
              12. Has been treated with any known drugs that are moderate or strong&#xD;
                  inhibitors/inducers of cytochrome P450 (CYP) enzymes (e.g., barbiturates,&#xD;
                  phenothiazines, cimetidine, carbamazepine) within 30 days before the first dose&#xD;
                  of study medication, and that, in the Investigator's judgment, may impact subject&#xD;
                  safety or the validity of the study results.&#xD;
&#xD;
                  Specifically, the use of any drugs known to inhibit CYP2C9 and CYP3A4 enzymes&#xD;
                  (examples include amiodarone, fluconazole, ketoconazole, itraconazole,&#xD;
                  clarithromycin, ritonavir, erythromycin, grapefruit or orange or apple juice) or&#xD;
                  any drugs that are highly protein-bound (for example, warfarin, cyclosporine,&#xD;
                  amphotericin B) within 30 days prior to the first dose of study medication, and&#xD;
                  that in the Investigator's judgment may impact subject safety or the validity of&#xD;
                  the study results.&#xD;
&#xD;
              13. Blood or plasma donation within 30 days before the first dose of study medication&#xD;
                  until the EOS. It is recommended that blood/plasma donations not be made for at&#xD;
                  least 30 days after the EOS.&#xD;
&#xD;
              14. Has any prior history of substance abuse or treatment (including alcohol).&#xD;
&#xD;
                    1. History of significant alcohol abuse within 6 months of Screening or any&#xD;
                       indication of the regular use of more than 2 units of alcohol per day (1&#xD;
                       unit = 50 mL of wine or 360 mL of beer or 45 mL of alcohol 40%).&#xD;
&#xD;
                    2. History of use of marijuana within 3 months of Screening or drugs such as&#xD;
                       cocaine, phencyclidine (PCP), within 1 year of Screening.&#xD;
&#xD;
              15. Smoking or use of tobacco- or nicotine-containing products within 60 days before&#xD;
                  the first dose of study medication until the EOS Note: Nonsmokers are preferred&#xD;
                  for this study.&#xD;
&#xD;
              16. Any food allergy, intolerance, restriction, or special diet that, in the opinion&#xD;
                  of the Investigator, contraindicates the subject's participation in this study.&#xD;
&#xD;
              17. Has been on a significantly abnormal diet during the 4 weeks preceding the first&#xD;
                  dose of study medication.&#xD;
&#xD;
              18. Consumption of beverages or foods that contain alcohol, grapefruit, poppy seeds,&#xD;
                  broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or&#xD;
                  caffeine/xanthine from 48 hours before the first dose of study medication until&#xD;
                  the EOS. Subjects will be instructed not to consume any of the above products;&#xD;
                  however, allowance for an isolated single incidental consumption may be evaluated&#xD;
                  and approved by the study Investigator based on the potential for interaction&#xD;
                  with the study drug.&#xD;
&#xD;
              19. Engagement in strenuous exercise from 48 hours before the first dose of study&#xD;
                  medication until the EOS.&#xD;
&#xD;
              20. A clinically significant abnormal finding on the physical examination, medical&#xD;
                  history, electrocardiogram (ECG), or clinical laboratory results at Screening.&#xD;
&#xD;
                  Note: Laboratory test values above or below the normal range does not necessarily&#xD;
                  indicate that the value is &quot;clinically significant.&quot; The determination should be&#xD;
                  made at the discretion of the Investigator with consultation, when necessary,&#xD;
                  with the Sponsor.&#xD;
&#xD;
              21. Presence of active infection, mucositis, cold sores, apthous ulcers, vesicles,&#xD;
                  viral lesions, local irritation/inflammation, or periodontal disease of the oral&#xD;
                  cavity. In addition, evidence of piercings of the tongue or anywhere in the oral&#xD;
                  cavity, history of oral cavity piercings, or history of significant dental&#xD;
                  disease or braces or oral hardware.&#xD;
&#xD;
              22. Clinically significant ECG abnormalities at Screening.&#xD;
&#xD;
              23. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ˃1.25&#xD;
                  times the upper limit of normal at Screening or Check-in for Period 1.&#xD;
&#xD;
              24. Is a female with a positive pregnancy test result.&#xD;
&#xD;
              25. Has a positive urine screen for drugs of abuse (amphetamines, barbiturates,&#xD;
                  benzodiazepines, cocaine, cannabinoids, opiates) or cotinine.&#xD;
&#xD;
              26. Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or&#xD;
                  human immunodeficiency virus (HIV) at Screening or has been previously treated&#xD;
                  for hepatitis B, hepatitis C, or HIV infection.&#xD;
&#xD;
              27. Has poor venous access during blood sampling at Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cynthia Zamora, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Worldwide Clinical Trials</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>WWCT</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>February 22, 2021</last_update_submitted>
  <last_update_submitted_qc>February 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04485702
org study id: MELT-100-001
nct id: NCT04485702
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Comparative Bioavailability study testing MELT-100 (midazolam and ketamine sublingual tablet)
      and IV midazolam or ketamine in healthy volunteers
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomized, Single-Dose, 6-Sequence, 3-Period, Crossover
primary purpose: Other
masking: Single (Participant)
masking description: randomization
measure: Peak Plasma Concentration (Cmax)
time frame: 24 hours
measure: Area under the plasma concentration versus time curve (AUC)
time frame: 24 hours
measure: Time to peak plasma concentration (Tmax)
time frame: 24 hours
arm group label: MELT-100
arm group type: Active Comparator
description: 3mg midazolam and 25mg ketamine sublingual tablet
arm group label: IV midazolam
arm group type: Active Comparator
description: 2mg Intravenous midazolam
arm group label: IV ketamine
arm group type: Active Comparator
description: 6mg Intravenous ketamine
intervention type: Drug
intervention name: Midazolam injection
description: 2mg IV
arm group label: IV midazolam
intervention type: Drug
intervention name: Ketamine Injectable Product
description: 6mg IV
arm group label: IV ketamine
intervention type: Drug
intervention name: MELT-100
description: midazolam 3mg and ketamine 25mg SL tablet
arm group label: MELT-100
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Cynthia Zamora, MD
role: Principal Investigator
affiliation: Worldwide Clinical Trials
facility: 
country: United States
responsible party type: Sponsor
mesh term: Midazolam
mesh term: Ketamine
sharing ipd: No