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

• ClinicalTrials.gov Identifier: NCT03880487
• Recruitment Status: Terminated
• First Posted: March 19, 2019
• Last Update Posted: September 16, 2021
• Sponsor: Kalyra Pharmaceuticals, Inc.
• Collaborators: United States Department of Defense; PRA Health Sciences
• Information provided by (Responsible Party): Kalyra Pharmaceuticals, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Analgesia	Drug: KP-1199; Drug: Placebo oral capsule; Drug: Oxycodone oral capsule	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: March 12, 2019
• Actual Primary Completion Date: April 21, 2020
• Actual Study Completion Date: April 21, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Pharmacokinetic Profile of KP-1199 to measure plasma concentration of KP-1199 [ Time Frame: 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) ]
   Maximum Observed Plasma Concentration (Cmax)
2. Pharmacokinetic Profile of KP-1199 to measure Time to Maximum plasma concentration of KP-1199 [ Time Frame: 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) ]
   Time to Maximum Plasma Concentration (Tmax)
3. Pharmacokinetic Profile of KP-1199 to measure area under curve plasma concentration of KP-1199 [ Time Frame: 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) ]
   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)
4. Pharmacokinetic Profile of KP-1199 to measure plasma terminal half-life concentration of KP-1199 [ Time Frame: 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) ]
   The Apparent Terminal Elimination Half-life (t1/2)
5. Pharmacokinetic Profile of KP-1199 to measure the trough plasma concentration of KP-1199 [ Time Frame: 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) ]
   Trough Plasma Concentration (Ctrough)
6. Pharmacodynamic Effects of KP-1199 using Cold Pressor Test to measure pain threshold [ Time Frame: Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration) ]
   Time to feel first pain ("pain threshold" measured in seconds)
7. Pharmacodynamic Effects of KP-1199 using Cold Pressor Test to measure pain tolerance [ Time Frame: Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration) ]
   Time to withdrawal of hand from cold water ("Pain tolerance" in seconds)
8. Pharmacodynamic Effects of KP-1199 using Cold Pressor Test [ Time Frame: Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration) ]
   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)"
9. Pharmacodynamic Effects of KP-1199 using Ultraviolet Burn Model (UVB) [ Time Frame: Part 3: Day 1, Day 3, Day 5 and Day 7 (pre-dose through 6 hours after dose administration) ]
   Neurosensory Testing (change in neurosensory assessments of the skin at site of ultraviolet burn)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Utah

PRA Health Sciences

Salt Lake City, Utah, United States, 84124

Sponsors and Collaborators

Kalyra Pharmaceuticals, Inc.

United States Department of Defense

PRA Health Sciences

Investigators

• Study Director: Kevin Bunker, PhD; Kalyra Pharmaceuticals, Inc.

More Information

• Responsible Party: Kalyra Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03880487
• Other Study ID Numbers: KP-1199-CP-001; CDMRP-OR 160158 ( Other Grant/Funding Number: Department of Defense )
• First Posted: March 19, 2019
• Last Update Posted: September 16, 2021
• Last Verified: February 2021

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

Keywords provided by Kalyra Pharmaceuticals, Inc.:

Phase I, Healthy Adult Participants

Additional relevant MeSH terms:

Oxycodone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents