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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)

Primary Purpose

Cataract

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

MELT-300

Midazolam alone

Ketamine alone

Placebo

About this trial

This is an interventional prevention trial for Cataract focused on measuring Cataract surgery, Intraocular pressure, Intraoperative ocular pain, Sedation, Lens replacement, MELT-300, Cataract extraction

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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).
Intraocular pressure (IOP) ≥ 23 mmHg in the study eye and/or ≥ 30 mmHg in the fellow eye at screening. This IOP exclusion requirement will only need to be re-confirmed on the day of surgery if it has been > 14 days since the screening visit.
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.

12. 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.

13. History of or presence of any connective tissue disorder (i.e., lupus, rheumatoid arthritis, fibromyalgia).

14. 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.
Antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days, or which is not expected to remain stable throughout the study.
15. Chronic pain rated moderate to severe within the past week (4-pt categorical scale, 0=no pain, 1=mild pain, 2=moderate pain, 3=severe pain). 17. Hospital Depression and Anxiety Scale (HADS) score > 10

Sites / Locations

Martel Eye Medical Group
Levenson Eye Associates
Vance Thompson Vision

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Arm Label

MELT-300

Midazolam alone

Ketamine alone

Placebo

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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 =Participant is anxious and agitated or restless, or both =Participant is cooperative, oriented, and tranquil =Participant responds to commands only =Participant exhibits brisk response to a light glabellar tap or loud auditory stimulus =Participant exhibits a sluggish response to a light glabellar tap or loud auditory stimulus =Participants exhibits no response RSS score will be assessed pre-operatively, intra-operatively, and post-operatively on 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")

Secondary Outcome Measures

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

Percentage of Analgesia Responders Using Numeric Pain Rating Scale

Number of Participants with Sedation Scores

Number of Participants with Pain Scores

Number of Participants-rated Worst Pain Following Completion of Surgery

Percentage of Participants Able to Complete Surgery

Percentage of Participants Without Interruption of Surgery for Intervention (Other Than Rescue Medication) Due to Pain or Anxiety

Percentage of Participants Requiring Rescue Sedative Medication

The preoperative target level of sedation for this trial is Ramsay Sedation Scale (RSS) 2 or 3. If a participant does not achieve this level of sedation prior to the start of surgery (administration of topical local anesthesia), rescue sedation medication (i.e., intravenous midazolam only, at a dose determined by Investigator or anesthesiologist) may be given. Use of rescue sedation medication during surgery will be allowed if a participant's RSS score is <2.

Percentage of Participants Requiring Rescue Analgesic Medication

Intraoperative pain assessments using the Numeric Pain Rating Scale (NPRS) scale, from 0 (no pain) to 10 (extreme pain), will be assessed. The 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").

Number of Participants Reported with At least One Treatment Emergent Adverse Event (TEAE)

A treatment-emergent adverse event is defined as any event not present prior to the initiation of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment.

Full Information

NCT ID

NCT05133518

First Posted

November 12, 2021

Last Updated

December 15, 2022

Sponsor

Melt Pharmaceuticals

Collaborators

Worldwide Clinical Trials

1. Study Identification

Unique Protocol Identification Number

NCT05133518

Brief Title

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)

Official Title

A Phase 2, Factorial-Designed, Randomized, Double-Blind, Placebo-Controlled, Parallel- Cohort Study to Evaluate Efficacy and Safety of MELT-300 and the Contribution of Midazolam and Ketamine Components to Sedation and Intraoperative Ocular Analgesia in Subjects Undergoing Cataract Extraction With Lens Replacement (CELR)

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

July 20, 2021 (Actual)

Primary Completion Date

October 26, 2022 (Actual)

Study Completion Date

November 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Melt Pharmaceuticals

Collaborators

Worldwide Clinical Trials

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

This is a Phase 2, factorial-designed, randomized, double-blind, placebo-controlled, parallel-cohort study to be conducted in 324 adult male and female participants who are ≥ 55 years of age and undergoing cataract extraction with lens replacement. An additional 3 participants per site (first 3 participants enrolled per site) will be considered sentinel participants for the purpose of ensuring safety and that logistical and operational challenges that may occur during the study are identified and mitigated. Sentinel participants will be evaluated for safety but not for efficacy. The study aims to evaluate the efficacy and safety of MELT-300 and the contribution of midazolam and ketamine components for procedural sedation prior to cataract surgery. In the study, eligible study participants will be randomly assigned (1:1:1:1 ratio) to one of the following treatments: MELT-300 (3 mg/50 mg), midazolam 3 mg, ketamine 50 mg, and placebo sublingual tablet 30 (± 5) minutes prior to the anticipated start of surgery (defined as instillation of topical ocular anesthetic drops [i.e., proparacaine]) without food or water in the operating room. At the time of dosing, participants will be instructed to hold the tablet under their tongue until it is completely dissolved and to not swallow or chew the tablets. The study duration will be up to 35 days, including 28 days for screening and 7 ± 2 days after surgery. Efficacy assessments will be performed after study medication administration before surgery, intraoperatively, and postoperatively on Day 1 (end of surgery defined as drape removal). Efficacy assessments will include assessments of sedation and intraoperative pain, the need for rescue medication for sedation or pain, and the ability to complete the surgery. Safety will be monitored at baseline, intraoperatively, postoperatively on Day 1, on the day after surgery (Day 2, via a phone call), and at 1 week (Day 8 ± 2 days) after dosing of study medication. Safety assessments will include monitoring of AEs, vital sign measurements, physical examinations, and 12-lead ECGs. Exploratory endpoints are postoperative pain as measured by the NPRS prior to discharge, 6 hours +/- 30 minutes after the end of surgery on Day 1 and on Days 2 (the day after surgery), the percentage of participants with concomitant medication opioid use, and average opioid consumption on Day 2 and participant likelihood of wanting study drug again for second cataract surgery as measured by an 11-point Likert scale on Day 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cataract

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

338 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MELT-300

Arm Type

Active Comparator

Arm Description

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

Arm Title

Midazolam alone

Arm Type

Active Comparator

Arm Description

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

Arm Title

Ketamine alone

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

MELT-300

Intervention Description

Sublingual tablet

Intervention Type

Drug

Intervention Name(s)

Midazolam alone

Intervention Description

Sublingual tablet

Intervention Type

Drug

Intervention Name(s)

Ketamine alone

Intervention Description

Sublingual tablet

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Sublingual tablet

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Day 1

Title

Mean Intraoperative Analgesia as Measured by the Numeric Pain Rating Scale

Description

Time Frame

Intraoperatively on Day 1

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

Percentage of Analgesia Responders Using Numeric Pain Rating Scale

Description

Time Frame

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

Title

Number of Participants with Sedation Scores

Description

Time Frame

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

Title

Number of Participants with Pain Scores

Time Frame

Before dosing on the day of surgery (Day 1)

Title

Number of Participants-rated Worst Pain Following Completion of Surgery

Time Frame

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

Title

Percentage of Participants Able to Complete Surgery

Time Frame

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

Title

Percentage of Participants Without Interruption of Surgery for Intervention (Other Than Rescue Medication) Due to Pain or Anxiety

Time Frame

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

Title

Percentage of Participants Requiring Rescue Sedative Medication

Description

Time Frame

Pre-operatively (at baseline) and Intra-operatively on Day 1

Title

Percentage of Participants Requiring Rescue Analgesic Medication

Description

Time Frame

After study medication administration before surgery (baseline) and intraoperatively

Title

Number of Participants Reported with At least One Treatment Emergent Adverse Event (TEAE)

Description

Time Frame

Pre-operatively (at baseline), intra-operatively post-operatively on Day 1, on the day after surgery (Day 2, via a phone call), and at 1 week (Day 8 ± 2 days) after dose of study medication

Other Pre-specified Outcome Measures:

Title

Postoperative Pain as measured by the Numeric Pain Rating Scale Scores

Description

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").

Time Frame

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

Title

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

Description

Concomitant medication is a medication, a person is taking that is not being studied in the clinical trial he or she is taking part in.

Time Frame

Day 2

Title

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

Description

A Likert Scale is a Psychometric Scale commonly involved in research that employs questionnaires. A Likert scale is the sum of responses on several Likert items. A Likert item is simply a statement that the respondent is asked to evaluate by giving it a quantitative value on any kind of subjective or objective dimension, with the level of agreement/disagreement being the dimension most commonly used. Study participants will be asked to rate their likelihood that they would want the same study medication again if they had second cataract surgery on an 11-point Likert scale of 0 (not likely at all) to 10 (extremely likely)

Time Frame

Day 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 1. Are to undergo unilateral primary uncomplicated CELR under topical anesthesia, with a phacoemulsification device and insertion of an intraocular lens. Exclusion Criteria: 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). Intraocular pressure (IOP) ≥ 23 mmHg in the study eye and/or ≥ 30 mmHg in the fellow eye at screening. This IOP exclusion requirement will only need to be re-confirmed on the day of surgery if it has been > 14 days since the screening visit. 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. 12. 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. 13. History of or presence of any connective tissue disorder (i.e., lupus, rheumatoid arthritis, fibromyalgia). 14. 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. Antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days, or which is not expected to remain stable throughout the study. 15. Chronic pain rated moderate to severe within the past week (4-pt categorical scale, 0=no pain, 1=mild pain, 2=moderate pain, 3=severe pain). 17. Hospital Depression and Anxiety Scale (HADS) score > 10

Facility Information:

Facility Name

Martel Eye Medical Group

City

Rancho Cordova

State/Province

California

ZIP/Postal Code

95670

Country

United States

Facility Name

Levenson Eye Associates

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32204

Country

United States

Facility Name

Vance Thompson Vision

City

W. Fargo

State/Province

North Dakota

ZIP/Postal Code

58078

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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)

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