A Single and Multiple Ascending Dose Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of KP-1199

A Randomized, Placebo- and Active-Controlled, Double-Blind, Single and Multiple Ascending Dose Study in Healthy Adults to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KP-1199

This is a Phase I, randomized, placebo and active-controlled, double blind, single and multiple ascending dose study in healthy adults to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of KP-1199

Study Overview

• Status: Terminated
• Conditions: Analgesia
• Intervention / Treatment: Drug: KP-1199; Drug: Placebo oral capsule; Drug: Oxycodone oral capsule

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Adult 18-45 years of age at time of screening, inclusive.
• Have a body mass index (BMI) between 18.0 and ≤32 kg/m2, inclusive, and a weight of ≥50 kg at screening.
• Be determined to be healthy on the basis of a pre-study physical examination, medical history review, vital sign measurements, and the results of laboratory tests.
• For both male and females: using acceptable method of birth control
• If Female: not-pregnant or not breast feeding and not planning on becoming pregnant
• All prescribed medication must have been stopped at least 14 days prior to admission to the clinical research site. An exception is made for hormonal contraceptives, which may be used throughout the study.
• All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (eg, St. John's Wort) must have been stopped at least 14 days prior to admission to the clinical research site.
• Must be adequately informed and understand the nature and risks of the study and must provide written informed consent prior to enrollment at screening.

Exclusion Criteria:

• Subjects who participate in one part of the study are not eligible to participate in subsequent parts of the study.
• Women who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after the follow-up visit.
• Males with female partners who are planning to attempt to become pregnant during this study or within 90 days after the follow-up visit.
• History or evidence of significant clinical or psychiatric disorder, condition, or disease that, in the opinion of the Investigator would pose an unacceptable risk to the subject safety or interfere with the study evaluations, procedures, or completion of the study.
• Documented congenital QT syndrome, and/or corrected QT interval (Fridericia correction; QTcF) at screening or first admission > 450 ms.
• Positive screening test for hepatitis B surface antigen, anti-hepatitis C virus antibodies or anti-human immunodeficiency virus 1 and 2 antibodies.
• History of drug allergy diagnosed by a physician.
• Use of tobacco within 30 days prior to the first study drug administration.
• History of alcohol consumption exceeding 2 standard drinks per day on average.
• Routine or chronic use of more than 0.5 grams of acetaminophen daily.
• History of donation of more than 450 mL of blood within 60 days prior to dosing in the clinical research site or planned donation before 30 days has elapsed since intake of study drug.
• Plasma or platelet donation within 7 days of dosing
• Use of any investigational drug or device within 30 days of the first dose of study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KP-1199	Drug: KP-1199; Single dose and Multiple ascending doses of KP-1199 oral capsules
Placebo Comparator: Placebo oral capsules	Drug: Placebo oral capsule; Single dose and Multiple dose identical to active treatment but without KP-1199.
Active Comparator: Oxycodone oral capsules	Drug: Oxycodone oral capsule; 10 mg Oxycodone Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment Emergent Adverse Events	Number of treatment related adverse events as determined by abnormal clinical laboratory tests, vitals signs, physical exam, ECG parameters	Part 1: From Day 1 through Day 6, Part 2: From Day 1 through Day 11, Part 3: From Day 1 through Day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Profile of KP-1199 to measure plasma concentration of KP-1199	Maximum Observed Plasma Concentration (Cmax)	Part 1: Day 1 (pre-dose through 4 hours after dose administration), Part 2: (pre-dose through Day 8), Part 3: (pre-dose through Day 7)
Pharmacokinetic Profile of KP-1199 to measure Time to Maximum plasma concentration of KP-1199	Time to Maximum Plasma Concentration (Tmax)	Part 1: Day 1 (pre-dose through 4 hours after dose administration), Part 2: (pre-dose through Day 8), Part 3: (pre-dose through Day 7)
Pharmacokinetic Profile of KP-1199 to measure area under curve plasma concentration of KP-1199	Area Under the Concentration-time Curve Up to Time (t), where t is the last point with concentrations above the lower limit of quantitation (AUC0-t) Area Under the Concentration-time Curve for 1 dosing interval of a multiple dose regimen (AUCtau)	Part 1: Day 1 (pre-dose through 4 hours after dose administration), Part 2: (pre-dose through Day 8), Part 3: (pre-dose through Day 7)
Pharmacokinetic Profile of KP-1199 to measure plasma terminal half-life concentration of KP-1199	The Apparent Terminal Elimination Half-life (t1/2)	Part 1: Day 1 (pre-dose through 4 hours after dose administration), Part 2: (pre-dose through Day 8), Part 3: (pre-dose through Day 7)
Pharmacokinetic Profile of KP-1199 to measure the trough plasma concentration of KP-1199	Trough Plasma Concentration (Ctrough)	Part 1: Day 1 (pre-dose through 4 hours after dose administration), Part 2: (pre-dose through Day 8), Part 3: (pre-dose through Day 7)
Pharmacodynamic Effects of KP-1199 using Cold Pressor Test to measure pain threshold	Time to feel first pain ("pain threshold" measured in seconds)	Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration)
Pharmacodynamic Effects of KP-1199 using Cold Pressor Test to measure pain tolerance	Time to withdrawal of hand from cold water ("Pain tolerance" in seconds)	Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration)
Pharmacodynamic Effects of KP-1199 using Cold Pressor Test	Pain tolerance will be measured at time of hand withdrawal using a 11-point (0-10) Numeric Pain Rating Scale (NPRS) where "0 (no pain) to 10 (worst pain)"	Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration)
Pharmacodynamic Effects of KP-1199 using Ultraviolet Burn Model (UVB)	Neurosensory Testing (change in neurosensory assessments of the skin at site of ultraviolet burn)	Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration)

Collaborators and Investigators

• Sponsor: Kalyra Pharmaceuticals, Inc.
• Collaborators: United States Department of Defense; PRA Health Sciences
• Investigators: Study Director: Kevin Bunker, PhD, Kalyra Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): April 21, 2020
• Study Completion (Actual): April 21, 2020

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Phase I, Healthy Adult Participants
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Oxycodone
• Other Study ID Numbers: KP-1199-CP-001; CDMRP-OR 160158 (Other Grant/Funding Number: Department of Defense)

Drug and device information, study documents

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