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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pain

Intervention / Treatment
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* Drug: CT001
* Drug: Placebo
* Drug: Sufentanil
* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT001<br> | Drug: CT001<br>* Intranasal<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Intranasal<br>|
| Active Comparator: Sufentanil 27 mcg<br> | Drug: Sufentanil<br>* Intranasal<br>|
| Active Comparator: Ketamine 27 mg<br> | Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 13 mcg<br> | Drug: Sufentanil<br>* Intranasal<br>|
| Active Comparator: Ketamine 13 mg<br> | Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 40 mcg<br> | Drug: Sufentanil<br>* Intranasal<br>|
| Active Comparator: Ketamine 40 mg<br> | Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 13 mcg/Ketamine 13 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 13 mcg/Ketamine 27 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 13 mcg/Ketamine 40 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 27 mcg/Ketamine 13 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 27 mcg/Ketamine 40 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 40 mcg/Ketamine 13 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 40 mcg/Ketamine 27 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|
| Active Comparator: Sufentanil 40 mcg/Ketamine 40 mg<br> | Drug: Sufentanil<br>* Intranasal<br>Drug: Ketamine<br>* Intranasal<br>|

What is the study measuring?
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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 |