A Study of MELT-300 (Midazolam and Ketamine Sublingual Tablets) for Sedation and Intraoperative Ocular Analgesia in Participants Undergoing Cataract Extraction With Lens Replacement (CELR)

NCT05133518 | Completed Phase 2 FDA Drug

• 1 other identifier: MELT-2-001
• Study Type: interventional
• Target: 338
• Locations: 1 country
• Sites: 3

Brief Summary

The primary purpose of the study is to evaluate the efficacy and safety of MELT-300 (Midazolam and Ketamine Sublingual Tablets) and the contribution of midazolam and ketamine components to sedation and during the surgery or ocular analgesia in participants undergoing cataract surgery with lens replacement.

Conditions

Cataract

Keywords

Cataract surgery; Intraocular pressure; Intraoperative ocular pain; Sedation; Lens replacement; MELT-300; Cataract extraction

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Success for Procedural Sedation by Using Ramsay Sedation Scale

  The Ramsay Sedation Scale (RSS) was the first scale to be defined for the sedated participants and was designed as a test of arousability. The Ramsay Scale provides three levels of 'awake' states (score 1-3) and three levels of 'asleep' states (score 4-6). A score of 2 (participant is cooperative, orientated, and tranquil) best fits an optimum sedation level based on the criteria of calm, comfortable, communicative, and cooperative participants. Ramsay Sedation Scale 1. =Participant is anxious and agitated or restless, or both 2. =Participant is cooperative, oriented, and tranquil 3. =Participant responds to commands only 4. =Participant exhibits brisk response to a light glabellar tap or loud auditory stimulus 5. =Participant exhibits a sluggish response to a light glabellar tap or loud auditory stimulus 6. =Participants exhibits no response RSS score will be assessed pre-operatively, intra-operatively, and post-operatively on Day 1

  Day 1

• Mean Intraoperative Analgesia as Measured by the Numeric Pain Rating Scale

  The Numeric Pain Rating Scale (NPRS) is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of his/her pain. The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")

  Intraoperatively on Day 1

Secondary Outcomes (10)

• Percentage of Pre-operative Target Sedation Responders by Ramsay Sedation Scale (level 2 or 3)

  Pre-operatively (at baseline), intra-operatively and post-operatively on Day 1

• Percentage of Analgesia Responders Using Numeric Pain Rating Scale

  Pre-operatively (at baseline), intra-operatively and post-operatively on Day 1

• Number of Participants with Sedation Scores

  After study medication administration before surgery (baseline), intraoperatively, and postoperatively on Day 1 (end of surgery defined as drape removal)

• Number of Participants with Pain Scores

  Before dosing on the day of surgery (Day 1)

• Number of Participants-rated Worst Pain Following Completion of Surgery

  Pre-operatively (at baseline), intra-operatively, and post-operatively on Day 1

Other Outcomes (3)

• Postoperative Pain as measured by the Numeric Pain Rating Scale Scores

  Prior to discharge, 6 hours +/- 30 minutes, and on Day 2 (the day after surgery)

• Percentage of Participants with Concomitant Medication Opioid Use and Average Opioid Consumption

  Day 2

• Participant Likelihood of Wanting Study Drug Again for Second Cataract Surgery as Measured by 11-point Likert Scale

  Day 2

Study Arms (4)

MELT-300

ACTIVE COMPARATOR

Participants will receive a single dose of MELT-300 sublingual, rapidly dissolving tablet containing 3 mg of midazolam and 50 mg of ketamine.

Drug: MELT-300

Midazolam alone

ACTIVE COMPARATOR

Participants will receive a single dose of midazolam 3 mg sublingual tablet.

Drug: Midazolam alone

Ketamine alone

ACTIVE COMPARATOR

Participants will receive a single dose of ketamine 50 mg sublingual tablet.

Drug: Ketamine alone

Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of a matching placebo sublingual tablet.

Drug: Placebo

Interventions

MELT-300 DRUG

Sublingual tablet

MELT-300

Midazolam alone DRUG

Sublingual tablet

Midazolam alone

Ketamine alone DRUG

Sublingual tablet

Ketamine alone

Placebo DRUG

Sublingual tablet

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Are to undergo unilateral primary uncomplicated CELR under topical anesthesia, with a phacoemulsification device and insertion of an intraocular lens.

You may not qualify if:

• Participants scheduled for simultaneous bilateral or 2nd-eye cataract surgery (note, subjects scheduled for a future 2nd eye cataract study are eligible for the study).
• Known sensitivity to benzodiazepines or ketamine.
• Known sensitivity to -caines (including proparacaine), benzalkonium chloride (BAK).
• History of iritis, or any ocular trauma with iris damage in the study eye.
• Presence of active corneal pathology other than corneal pathology per slit lamp and an external eye exam at screening in either eye.
• Presence of extraocular/intraocular inflammation in either eye.
• Presence of active bacterial and/or viral infection in either eye.
• History of intraocular non-laser surgery in the study eye within the 3 months prior to day of surgery, or intraocular laser surgery in the study eye within 30 days prior to the day of surgery.
• Require or are planning other additional ocular surgery during the cataract surgery.
• \. Have a history or clinical manifestations (e.g., signs, symptoms, laboratory values, diagnostic imaging, etc.) of significant gastrointestinal, cardiovascular, hepatic, renal, hematological, endocrine, neurological, psychiatric, respiratory, or other medical condition that in the opinion of the investigator might confound the study results or pose additional risk in administering the study procedures.
• \. History of or presence of any connective tissue disorder (i.e., lupus, rheumatoid arthritis, fibromyalgia).
• \. Use of disallowed medications, including the following:
• Pain medication (opioids, non-steroidal anti-inflammatory drugs \[NSAIDs\], cyclooxygenase-2 \[COX-2\] inhibitors, tramadol, ketamine, clonidine, gabapentin, pregabalin, or cannabinoids) within 3 days prior to Day 1, or routine, daily opioid therapy within the past 30 days.
• Central nervous system (CNS) active drugs such as benzodiazepines, tricyclic antidepressants, serotonin, and norepinephrine reuptake inhibitors (SNRIs), or selective serotonin reuptake inhibitors (SSRIs) for pain within 7 days prior to Day 1. These drugs are permitted for non-pain indications if the dose has been stable for at least 30 days prior to Day 1 and is planned to remain stable throughout the study. The use of lorazepam and other sleep medications, except those containing analgesic properties, is permitted.
• Use of parenteral or oral corticosteroid(s) within 14 days prior to Day 1.

Sponsors & Collaborators

• Melt Pharmaceuticals: lead
• Worldwide Clinical Trials: collaborator

Study Sites (3)

Martel Eye Medical Group

Rancho Cordova, California, 95670, United States

Location

Levenson Eye Associates

Jacksonville, Florida, 32204, United States

Location

Vance Thompson Vision

West Fargo, North Dakota, 58078, United States

Location

MeSH Terms

Conditions

Cataract

Interventions

Midazolam; Ketamine

Condition Hierarchy (Ancestors)

Lens Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Factorial-designed, randomized, double-blind, placebo-controlled, parallel-cohort safety and efficacy study.

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: November 24, 2021
• Study Start: July 20, 2021
• Primary Completion: October 26, 2022
• Study Completion: November 3, 2022
• Last Updated: December 19, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)