Single and Multiple Ascending Doses Clinical Pharmacology Study With KAR5585

NCT02746237 | Completed Phase 1

• 1 other identifier: KAR5585-101
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Safety, tolerability, pharmacokinetics (PK), cardiac conduction and food effect study on single and multiple ascending doses of KAR5585 in healthy adults.

Conditions

Pulmonary Arterial Hypertension

Keywords

Serotonin; Pulmonary Arterial Hypertension; Pharmacokinetics; Phase 1; Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• Number of participants with abnormal physical exam results

  Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via physical examination.

  From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses

• Number of participants with abnormal hematology values

  Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via lab evaluation of hematology.

  From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses

• Number of participants with abnormal electrocardiogram results

  Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for abnormal ECG results.

  From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses

• Number of participants with abnormal clinical chemistry values

  Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via lab evaluation of clinical chemistries.

  From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses

• Number of participants with abnormal urinalysis values

  Healthy adult volunteers receiving single and multiple doses of KAR5585 administered orally will be monitored for adverse events via lab evaluation of urinalysis.

  From baseline to 4 days post-dose for single dose and baseline to 6 days post-dose for multiple doses

Secondary Outcomes (15)

• Plasma area under the curve (AUC0-24) of prodrug KAR5585 and active inhibitor KAR5417 from time zero to 24 hours after dosing

  From 0-24 hours on Days 1, 7 and 14

• Time to reach maximum observed plasma concentration (Tmax) of prodrug KAR5585 and active inhibitor KAR5417

  From 0-24 hours on Days 1, 7 and 14

• Plasma terminal elimination half- life (T1/2) of prodrug KAR5585 and active inhibitor KAR5417

  From 0-24 hours on Days 1, 7 and 14

• Apparent volume of distribution (Vz/F) of prodrug KAR5585 and active inhibitor KAR5417

  From 0-24 hours on Days 1, 7 and 14

• Maximum peak concentration (Cmax) of prodrug KAR5585 and active inhibitor KAR5417

  From 0-24 hours on Days 1, 7 and 14

Study Arms (2)

KAR5585

EXPERIMENTAL

KAR5585 Capsules

Drug: KAR5585 Capsules

Placebo

PLACEBO COMPARATOR

Placebo capsules

Drug: Placebo Capsules

Interventions

KAR5585 Capsules DRUG

Single and multiple ascending doses of KAR5585 (100 mg initial dose)

Also known as: KAR5585

KAR5585

Placebo Capsules DRUG

Single and multiple ascending doses of placebo (100 mg initial dose)

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is able to read, write, and comprehend English at a sufficient level to understand study-related materials
• Subject is able to provide written informed consent and to comply with all study requirements and restrictions
• Subject is male or female and aged 18 to 65 years, inclusive, at the time of informed consent
• Subject is in good health as determined by the PI based on detailed medical history, physical examination, vital signs, clinical laboratory tests, ECGs, and other pre-dose evaluations
• Subject agrees to use a medically acceptable form of birth control from CRU admission until at least 30 days (female subject) or 90 days (male subject) after the last dose of study drug. Males will also not donate sperm from CRU admission until at least 90 days after the last dose of study drug. If a subject is not sexually active but becomes active during study participation, the subject agrees they and their partner will use a medically accepted form of contraception for the time specified. Medically acceptable forms of contraception are:
• FDA-approved female hormonal contraceptives used consistently for 2 or more cycles before Screening, including oral contraceptives, intrauterine device (IUD), medroxyprogesterone acetate injection (Depo Provera®), hormonal implant (Norplant®, Implanon®, Nexplanon®), and vaginal ring (NuvaRing®)
• Male condom plus spermicide
• Male condom plus contraceptive sponge, foam, or jelly
• Female condom plus spermicide
• Diaphragm with spermicide plus male condom
• Cervical cap with spermicide plus male condom
• Surgical sterilization of the subject or partner (vasectomy for males, hysterectomy or bilateral oophorectomy for females)
• Abstinence
• If female, subject agrees that a serum pregnancy test (\[β hCG\] beta human chorionic gonadotropin ) will be performed at Screening, on Day 2 (CRU admission), and at the last study visit and negative test results at Screening and CRU admission are required to be considered for study participation
• Subject has a body mass index (BMI) of 20 to 35 kg/m2, inclusive, and body weight \< 120 kg at Screening

You may not qualify if:

• Subject currently uses tobacco or nicotine-containing products or has used such products within 6 months before CRU admission
• Subject has history or current evidence of any clinically significant cardiac, endocrinologic, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the PI
• Subject has a history of cancer within 5 years before CRU admission (excluding non-melanoma skin cancer)
• Subject has a history of autonomic dysfunction (eg, history of repeated dizziness, fainting, or symptomatic orthostatic hypotension)
• Subject has a history of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, OR clinically significant abnormal laboratory assessments including hypokalemia, hypomagnesemia, or hypercalcemia OR has a family history of long QT syndrome or Brugada syndrome
• Subject has 1 or more clinically significant abnormal laboratory test values (as determined by the PI)
• Subject has an uninterpretable or abnormal screening ECG indicating a second- or third-degree atrioventricular block, or 1 or more of the following: QRS interval (ventricular depolarization) \> 110 msec; a PR interval (atrioventricular conduction) \> 220 msec, or QTc (corrected QT interval) of ≥ 450 msec (for male) or ≥ 470 msec (for female) or any rhythm other than sinus rhythm that is interpreted by the PI or a qualified designee to be clinically significant
• Subject has a resting heart rate (HR) of \< 40 beats/min or \> 90 beats/min at Screening or on CRU admission
• Subject has a sustained supine systolic blood pressure (BP) \> 155 or \< 90 mm Hg or a supine diastolic BP \> 95 or \< 50 mm Hg at Screening or upon CRU admission. Blood pressure in the supine position may be retested once and 'sustained' is defined as the parameter (either systolic or diastolic BP) being outside the stated limits at both assessments.
• Subject participates in another clinical trial or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer, before CRU admission
• Subject has a history of alcohol or drug abuse or dependence within 12 months before CRU admission, as determined by the PI
• Subject has a clinically significant infection within 3 months before CRU admission, as determined by the PI
• Subject has any condition that, in the opinion of the PI, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study
• Subject has a positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine \[urine cotinine is the detection mechanism for nicotine\], opiates, barbiturates, amphetamines, and benzodiazepines) or positive urine test for alcohol
• Subject has a positive blood screen for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus antibody at the Screening Visit

Sponsors & Collaborators

• Karos Pharmaceuticals: lead

Study Sites (1)

Spaulding Clinical

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

rodatristat

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Carlos Sanabria, MD

  Spaulding Clinical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: April 21, 2016
• Study Start: November 1, 2015
• Primary Completion: May 1, 2016
• Study Completion: August 1, 2016
• Last Updated: August 30, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)