Pharmacokinetics and Safety of MNK-155 in Postsurgical Adolescent Subjects With Moderate to Severe Acute Pain

NCT02767349 | Withdrawn Phase 1

• 1 other identifier: MNK15041015
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label study of the pharmacokinetics (PK) and safety of MNK-155 in postsurgical adolescent subjects aged 12 to 17 years with moderate to severe acute pain. The study will assess the safety of administering multiple doses of MNK-155 in this population.

Conditions

Acute Pain

Outcome Measures

Primary Outcomes (5)

• Time to reach steady state

  12 Hours

• Area under the curve

  Area under the concentration time curves after the first and last dose

  12 Hours

• Peak exposure

  12 Hours

• Half-life

  Apparent elimination half-life

  12 Hours

• Time to peak exposure

  Observed time when peak exposure occurred

  12 Hours

Study Arms (1)

MNK-155

EXPERIMENTAL

MNK-155, initial dose of two or three tablets followed by 2 tablets every 12 hours up to a maximum of five doses.

Drug: MNK-155

Interventions

MNK-155 DRUG

2 or 3 tablets initial dose, followed by two tablets every twelve hours

MNK-155

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject must be male or nonpregnant, nonlactating females between 12 and 17 years of age (inclusive) at time of screening.
• Subject must have a minimum weight of 100 pounds (45 kg) at the time of screening and have a body mass index (BMI) \> 5% and \< 95% for their age at the time of screening.
• Subject must report having moderate or severe acute pain (as determined from the Numerical Pain Rating scale (NPRS) where 0 = no pain, 10 = worst pain; subjects must have a level of 4 or more) after a pediatric surgical procedure (at baseline) that requires hospitalization. Sponsor will pre-approve a list of acceptable surgical procedures prior to study start for each site. Surgical procedures other than those on the pre-approved list may be acceptable on a case by case basis if approved by the medical monitor (MM) and sponsor.
• Subject, if female of child-bearing potential (defined as postmenarche), must agree to abstain from unprotected sexual activity during study participation and for 2 weeks after study exit/early termination.
• Subject, if male with reproductive potential, must agree to abstain from unprotected sexual activity during study participation and for 2 weeks after study exit/early termination.
• Subject, if female of childbearing potential, must have negative pregnancy test (serum or urine) results at screening and check-in.
• Subject's legally authorized representative (eg, parent, legal guardian) must voluntarily sign and date a parental permission/ Informed Consent that is approved by an Institutional Review Board (IRB), and the subject must sign an IRB approved assent, before undergoing any protocol specific procedures or assessments.
• Subject and the subject's parent or legal guardian must be able to read, understand, and be willing to follow the study procedures and requirements and communicate meaningfully in English with the investigator and investigator's staff (if the subject cannot read or communicate meaningfully, then the subject's legally authorized representative \[eg, parent, legal guardian\] must meet this criterion).

You may not qualify if:

• Subject is from a vulnerable population (including mentally disabled children), other than a pediatric population, as defined by the Code of Federal Regulations Title 45, Part 46, Section 46.111(b), including but not limited to employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the clinical research organization, or of the IRB.
• Subject is expected to require a surgery that could influence the study outcome (eg, ventriculoperitoneal shunt repair in the setting of hydrocephalus).
• Subject has an abnormal electrocardiogram (ECG) unless the investigator determines the ECG abnormalities are not clinically significant.
• Subject has a screening pulse oximetry reading of \< 95% while awake.
• Subject has a history of laboratory test results obtained before screening that show the presence of human immunodeficiency virus (HIV), hepatitis B surface antigen, hepatitis C antibody, or active hepatitis A immunoglobulin M.
• Subject has laboratory values that are greater than 2 times the upper limit of normal (with the exception of white blood cell \[WBC\] differential values). Enrollment of subjects with laboratory values that are between 1 and 2 times the upper limit of normal (ULN), or below the lower limit of normal, or white blood cells (WBC) differential \> 2 x ULN , will be left to the investigator's discretion (no increased risk of participation in study based upon judgment of the investigator).
• Subject has any history of renal disease that, in the opinion of the investigator, would contraindicate study participation; or subject has significantly impaired renal function, in the opinion of the investigator as evidenced by an estimated glomerular filtration rate calculated using a pediatric appropriate formula such as the Schwartz Equation (Schwartz et al, 2009).
• Subject has a history or laboratory evidence of bleeding or clotting disorders or conditions.
• Subject has a known or suspected history of alcoholism, marijuana or illicit drug abuse or misuse within 2 years before screening as evidence from medical history or evidence of tolerance or physical dependence before the first dose of MNK-155.
• Subject has smoked or used nicotine-containing products within 6 months prior to screening as evidenced by medical history.
• Subject has a history of psychiatric disorders, such as major depression disorder, anxiety disorders, or psychotic disorders requiring hospitalization and/or medication within 6 months prior to screening. A history of attention deficit hyperactivity disorder requiring medication is acceptable.
• Subject has a diagnosis of epilepsy or other seizure disorder (a history of febrile seizures is acceptable).
• Subject has had previous cardiothoracic surgery (subjects who have a history of patent ductus arteriosus ligations/surgery as infants are acceptable).
• Subject has a history of conditions which might be specifically contraindicated or require caution while using hydrocodone bitartrate (HB), acetaminophen (APAP), and/or ibuprofen (if used as rescue medication) per the Investigator's Brochure (IB) and product information per the appropriate package insert.
• Subject has a history of any drug allergy, hypersensitivity, or intolerance including HB, APAP, ibuprofen or excipients, or any opioid drug product which, in the opinion of the investigator, would place the subject at particular risk and compromise the safety of the subject in the study.

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (1)

Duke University Health Systems

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2016
• First Posted: May 10, 2016
• Study Start: January 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: June 1, 2017
• Last Updated: April 5, 2017

Record last verified: 2017-04

Locations

US (1)