A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of KUR-101 in Healthy Adults

Study Overview
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Brief Summary
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This project is testing the safety, tolerability, pharmacokinetics (PK, the amount of study drug in your blood) and pharmacodynamics (PD, how the study drug affects your body) of single doses of a new drug called KUR-101. Up to 58 healthy men or women aged between 18-55 will be enrolled in this study in two parts. Part 1 will involve a single ascending (increasing) dose (SAD) where 40 participants (5 groups of 8) will be randomised (assigned randomly, like flipping a coin) to receive a single oral dose of the study drug or placebo. The placebo will look the same as the study drug but will not contain any medicine. Part 2: will involve a crossover design where 18 participants will be randomised to receive a single oral dose of each of three interventions (study drug, placebo or a marketed form of oxycodone). Each dose is separated by 7 days and the participants are randomised so they do not know the order of the interventions. For Part 1 the total participation will last 9 days, of which 4 days (3 nights) will be spent in the clinic. One group of subjects in Part 1 will return to the clinic to receive a second dose of drug given with a high fat breakfast. In this group, the total participation will last 16 days, of which 8 days (7 nights) will be spent in the clinic. For Part 2 the total participation will last 23 days, of which 9 days (8 nights) will be spent in the clinic.

Detailed Description
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This is a Phase 1, single-center, prospective, study of orally administered KUR-101 in normal healthy participants. The study will be conducted in two parts. Part 1 is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, PK, analgesic and respiratory effects of single ascending doses of orally administered KUR-101 in normal healthy participants. Once the MTD has been determined, this dose, or an alternate lower dose, will be taken into Part 2 of the study. Part 2 is a randomized, double-blind, placebo-controlled, three-period crossover study to assess the analgesic and respiratory effects of a single oral KUR-101 as compared to that of oxycodone in normal healthy participants.

Official Title
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A Phase 1 Randomized, Double-Blind, Two Part Study of the Safety, Tolerability, Pharmacokinetics, Analgesic and Respiratory Effect of KUR-101 in Healthy Adult Participants

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: KUR-101
* Drug: OxyNorm
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects; Between 18 and 55 years of age; Provide a signed EC-approved consent form; Generally healthy, in the opinion of the Investigator; Body Mass Index (BMI) 18 to 32 kg/m^2; Using method of contraception; Willing and able to comply with protocol requirements for the duration of the study Exclusion Criteria: Subjects taking prohibited medications; Subjects with a history or presence of clinically significant medical or psychiatric disease; Subjects with a history of recreational or opiate use; Subjects with a history of alcohol abuse or moderate to severe substance abuse; Subjects who have regularly used nicotine-containing products; Subjects with a hospital admission or major illness within 1 month prior to Screening; Subjects with a major surgery within 3 months prior to Screening; Subjects who are pregnant or breastfeeding Subjects who have participated (taken investigative drug and/or device) in another clinical trial within 30 days prior to Screening; Subjects who belong to a vulnerable population.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Single ascending dose<br>Single dose of oral KUR-101 or oral placebo | Drug: KUR-101<br>* Single oral dose of KUR-101<br>Drug: Placebo<br>* Single oral dose of placebo<br>|
| Experimental: Part 2: Three-way crossover<br>Single dose of oral KUR-101, oral placebo and oral OxyNorm | Drug: KUR-101<br>* Single oral dose of KUR-101<br>Drug: OxyNorm<br>* Single oral dose of OxyNorm<br>Drug: Placebo<br>* Single oral dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Safety of KUR-101 when compared with placebo | Measured by the incidence of treatment-emergent adverse events | From the signing of the informed consent through Day 8 in Cohort 1, 2, 4 and 5 and through Day 15 in Cohort 3 | 
| Part 2: Effect of KUR-101 on evoked pain response as compared to oxycodone and placebo | Measured using the cold pressor test | Up to 4 hours post dose | 
| Part 2: Effect of KUR-101 on evoked pain response as compared to oxycodone and placebo | Measured using thermal sensory testing | Up to 4 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Pharmacokinetics of KUR-101 | Measured by levels of KUR-101 in the blood | Up to 48 hours post dose | 
| Part 1: Pharmacokinetics of KUR-101 | Measured by levels of KUR-101 in the urine | Up to 48 hours post dose | 
| Part 1: Effect of KUR-101 on respiratory function when compared to placebo | Measured using continuous end-tidal capnography monitoring | Up to 8 hours post dose | 
| Part 1: Effect of KUR-101 on respiratory function when compared to placebo | Measured using pulse oximetry | Up to 8 hours post dose | 
| Part 1: Effect of KUR-101 on respiratory function when compared to placebo | Measured using vital signs monitoring | Up to 8 hours post dose | 
| Part 2: Effect of KUR-101 on respiratory function when compared to placebo and oxycodone | Measured using continuous end-tidal capnography monitoring | Up to 8 hours post dose | 
| Part 2: Effect of KUR-101 on respiratory function when compared to placebo and oxycodone | Measured using pulse oximetry | Up to 8 hours post dose | 
| Part 2: Effect of KUR-101 on respiratory function when compared to placebo and oxycodone | Measured using vital signs monitoring | Up to 8 hours post dose | 
| Part 2: Safety of KUR-101 when compared with placebo and oxycodone | Measured by the incidence of treatment-emergent adverse events | From the signing of the informed consent through Day 22 | 
| Part 2: Addictive potential of KUR-101 when compared with placebo and oxycodone | Measured through the Desire for Opioids visual acuity scale | Up to 4 hours post dose | 
| Part 2: Addictive potential of KUR-101 when compared with placebo and oxycodone | Measured through the Addiction Research Center Inventory Morphine Benzedrine Group scale | Up to 4 hours post dose |