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

• ClinicalTrials.gov Identifier: NCT05114265
• Recruitment Status: Completed
• First Posted: November 9, 2021
• Last Update Posted: December 14, 2022
• Sponsor: Kures, Inc.
• Information provided by (Responsible Party): Kures, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acute Pain	Drug: KUR-101; Drug: OxyNorm; Drug: Placebo	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 15, 2022
• Actual Primary Completion Date: October 12, 2022
• Actual Study Completion Date: October 12, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: Single ascending dose; Single dose of oral KUR-101 or oral placebo	Drug: KUR-101; Single oral dose of KUR-101; Drug: Placebo; Single oral dose of placebo
Experimental: Part 2: Three-way crossover; Single dose of oral KUR-101, oral placebo and oral OxyNorm	Drug: KUR-101; Single oral dose of KUR-101; Drug: OxyNorm; Single oral dose of OxyNorm; Drug: Placebo; Single oral dose of placebo

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Part 1: Effect of KUR-101 on evoked pain response as compared to placebo [ Time Frame: Day 1 up to 4 hours post dose ]
   Measured using the cold pressor test
2. Part 1: Addictive potential of KUR-101 when compared with placebo [ Time Frame: Up to 4 hours post dose ]
   Measured through the Desire for Opioids visual acuity scale
3. Part 1: Addictive potential of KUR-101 when compared with placebo [ Time Frame: Up to 4 hours post dose ]
   Measured through the Addiction Research Center Inventory Morphine Benzedrine Group scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

New Zealand

KUR-101-101 Clinical Research Site

Christchurch, New Zealand, 8011

Sponsors and Collaborators

Kures, Inc.

More Information

• Responsible Party: Kures, Inc.
• ClinicalTrials.gov Identifier: NCT05114265
• Other Study ID Numbers: KUR-101-101
• First Posted: November 9, 2021
• Last Update Posted: December 14, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Acute Pain; Pain; Neurologic Manifestations