Efficacy and Pharmacokinetic-Pharmacodynamic Relationship of Intranasally Administered Sufentanil, Ketamine, and CT001

Analgesic Efficacy and Pharmacokinetic-pharmacodynamic Relationship of Intranasally Administered Sufentanil, Ketamine, and CT001 After Impacted Mandibular Third Molar Extraction - A Double-blind, Randomised, Placebo-controlled Study

A randomised, double-blind, parallel-group, study comparing the analgesic effect of intranasal CT001 to intranasal sufentanil, intranasal ketamine or placebo for treatment of acute pain in adults undergoing surgical removal of an impacted mandibular third molar, where bone removal is judged to be needed.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: CT001; Drug: Placebo; Drug: Sufentanil; Drug: Ketamine

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jes Trygved; Phone Number: +45 93872309; Email: Jes.Trygved@cessatech.com

Study Locations

• Denmark
  • NV
    • Copenhagen, NV, Denmark, 2400
      • DanTrials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Healthy (The American Society of Anaesthesiologists' Physical Classification System (ASA) I-II) male or female participants scheduled for surgical removal of an impacted mandibular third molar, where bone removal is judged to be needed
• Age: ≥ 18 and < 56 years
• Body Mass index above (>)18.5 or below (<) 30.0 kg/m2
• Prior to randomisation: Numeric Pain Rating Scale (NRS anchored by 0 = "no pain", 10 = "worst pain imaginable") ≥ 5 at rest within 4 hours after the administration of the last dose of local anaesthetic

Exclusion Criteria:

• Current or history of any clinically significant disease or disorder, which, in the opinion of the investigator, may put the potential subject at risk when participating in the study, or influence the potential subject's ability to participate in the study or influence the study results.
• Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of investigational product that is likely to introduce additional risk factors, jeopardize study integrity, or to interfere with the study assessments or procedure
• History of increased bleeding tendency
• Clinically significant mental illness
• Opioid Risk Tool score of >3
• Pain Catastrophizing Scale score, total points >30
• Hospital Anxiety and Depression Scale (HADS), points ≥ 11 for anxiety or ≥ 11 points for depression
• Daily intake of analgesics
• History of alcohol or drug abuse or use of illicit drugs or positive screen for drugs of abuse at screening or on admission to the Clinic prior to the administration of the investigational product.
• Abnormal nasal cavity/airway

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Intranasal
Experimental: CT001	Drug: CT001; Intranasal
Active Comparator: Sufentanil 27 mcg	Drug: Sufentanil; Intranasal
Active Comparator: Ketamine 27 mg	Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 13 mcg	Drug: Sufentanil; Intranasal
Active Comparator: Ketamine 13 mg	Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 40 mcg	Drug: Sufentanil; Intranasal
Active Comparator: Ketamine 40 mg	Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 13 mcg/Ketamine 13 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 13 mcg/Ketamine 27 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 13 mcg/Ketamine 40 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 27 mcg/Ketamine 13 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 27 mcg/Ketamine 40 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 40 mcg/Ketamine 13 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 40 mcg/Ketamine 27 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal
Active Comparator: Sufentanil 40 mcg/Ketamine 40 mg	Drug: Sufentanil; Intranasal; Drug: Ketamine; Intranasal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of pain intensity differences at 55 min	Derived from pain intensity scores measured by the Numerical Rating Scale (0-10, 0= no pain, 10= worst possible pain).	0-55 min
PK-PD relationship for analgesic efficacy IN sufentanil, IN ketamine and IN CT001	To assess the relationship between analgesic efficacy and the plasma concentrations of intranasal sufentanil, intranasal ketamine and intranasal CT001.	0-180 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Pain intensity difference (PIDmax)		0-180 min
Time to meaningful pain relief	Time when participants feel that the pain relief becomes meaningful to them	0-180 min
Sum of pain intensity differences at 30 min	Derived from pain intensity scores measured on the Numerical Rating Scale (0-10, 0= no pain, 10= worst possible	0-30 min
Rescue medication	Number of participants receiving rescue medication	0-180 min
Number of patients who are considered a responder/non-responder, 30%	Number of participants with at least 30% reduction in pain intensity score compared to baseline	0-30 min
Number of patients who are considered a responder/non-responder, 50%	Participants with at least at least 50% reduction in pain intensity score compared to baseline	0-30 min
Sum of pain intensity differences at 90 min	Derived from pain intensity scores measured on the Numerical Rating Scale (0-10, 0= no pain, 10= worst possible	0-90 min
Time to perceptible pain relief	Time when participants feel that the pain relief becomes meaningful to them	0-180 min
Time to rescue medication		0-180 min
Mean pain intensity difference (PID) from baseline at rest		0-180 min
Mean pain intensity difference (PID) from baseline on jaw movement		0-181 min
Ramsay sedation score	Change from baseline in Ramsay sedation score (1= agitated, anxious, restless, 6= unarousable)	0-179 min
Median time to a request for rescue medication		0-180 min

Collaborators and Investigators

• Sponsor: Cessatech A/S

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2022
• Primary Completion (Actual): October 5, 2023
• Study Completion (Actual): October 5, 2023

Study Registration Dates

• First Submitted: August 17, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: May 1, 2023

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; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Ketamine; Sufentanil
• Other Study ID Numbers: PDC 01-0205

Drug and device information, study documents

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