Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC

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Brief Title

Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC

Official Title

Randomized, Placebo-controlled, Double-blind, Dose Escalation Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC in Single Doses in Male and Female Subjects

Brief Summary

      This study is a single-center, randomized, placebo-controlled, double-blind, single ascending
      dose escalation study to determine the safety, tolerability, and PK profile of oral
      administration of HPN-07 in single doses to approximately 32 healthy male and female subjects
      between 18 and 55 years of age.

      Subjects will receive single oral doses of the study drug. The primary endpoint of this trial
      is to establish the safety and tolerability of HPN-07 and HPN-07 plus N-acetylcysteine (NAC).
    

Detailed Description

      This study is a single-center, randomized, placebo-controlled, double-blind, single ascending
      dose escalation study to determine the safety, tolerability, and PK profile of oral
      administration of HPN-07 in single doses to healthy male and female subjects between 18 and
      55 years of age.

      Approximately 32 subjects will be enrolled in a panel of 4 cohorts with approximately 8
      subjects per cohort. There will be approximately 3 sequential ascending dosing levels of
      HPN-07, with each cohort administered 1 dose of HPN-07 ranging from 500 mg to 1,500 mg and
      the fourth cohort administered the highest tolerated dose of HPN-07 plus 1,200 mg NAC.

      The primary endpoint of this trial is to establish the safety and tolerability of HPN-07 and
      HPN-07 plus N-acetylcysteine (NAC). Pharmacokinetics (PK) analysis of HPN-07 will enable a
      preliminary determination of the relationship between dose and the time course of the drug
      concentration in the body. Blood samples will be collected at regular intervals over the
      predicted time of HPN-07 systemic exposure.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Safety and tolerability of single doses of HPN-07, alone and in co-administration with NAC: Adverse events

Secondary Outcome

 Area under the curve (AUC) of single doses of HPN-07, alone and in co-administration with NAC

Condition

Hearing Loss

Intervention

HPN-07

Study Arms / Comparison Groups

 HPN-07 500 mg / Placebo
Description:  Single dose of 500mg HPN-07 plus placebo in oral capsules.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

32

Start Date

October 2014

Completion Date

February 2015

Primary Completion Date

January 2015

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female subjects, 18-55 years of age (inclusive), at the time of enrollment.

          -  Healthy as judged by a responsible physician with no clinically significant
             abnormality identified on the medical or laboratory evaluation, including 12-lead
             electrocardiogram (ECG). A subject with a clinical abnormality or laboratory
             parameters outside the reference range for this age group may be included only if the
             Investigator considers that the finding will not introduce additional risk factors and
             will not interfere with the study procedures (as defined as the research site's
             standard operating procedures).

          -  Male subjects who are surgically sterile OR agree to abstain from sexual intercourse
             with a female partner OR agree to use a condom and spermicide during sexual
             intercourse with a female partner who meets the following criteria: 1) uses another
             form of contraception, such as an intrauterine device (IUD), occlusive cap (diaphragm
             or cervical/vault cap) with spermicide, oral contraceptives, injectable progesterone,
             subdermal implants, female condom, contraceptive patch, or contraceptive vaginal ring;
             and/or 2) has had a tubal ligation or hysterectomy. These criteria must be followed
             from the time of the first dose of study medication until 14 days after the last dose
             of study medication. Men must also abstain from sperm donation from the time of the
             first dose of study medication until 14 days after the last dose of study medication.

          -  Female subjects of childbearing potential must be practicing abstinence or are using,
             and willing to continue using, a medically acceptable form of birth control for at
             least 1 month prior to Screening (at least 3 months for hormonal contraceptives) and
             for at least 2 months after the last study drug administration. Medically acceptable
             forms of contraception include abstinence, hormonal contraceptives (oral, patch or
             vaginal ring), intrauterine device, progestin implant or injection, bilateral tubal
             ligation, or double-barrier methods (i.e., male condom in addition to a diaphragm or a
             contraceptive sponge).

          -  Female subjects of non-childbearing potential, defined as: having undergone successful
             surgical sterilization (hysterectomy and/or bilateral
             oophorectomy/salpingo-oophorectomy, as determined by subject medical history) or
             post-menopausal. Postmenopausal is defined as being amenorrheic for at least 1 year
             without another cause and a follicle-stimulating hormone (FSH) level ~50 mlU/ml.

          -  Female subjects must have a negative pregnancy test at screening and Day -1
             (admission).

          -  Minimum body weight of 50.0 kg and body mass index (BMI) between 18.0 kg/m2 and 33.0
             kg/m2 (inclusive).

          -  Non-smoker (refrained from any tobacco usage, including smokeless tobacco, nicotine
             patches, etc:, for 6 months prior to the administration of the study medication) and
             has negative findings on a breath carbon monoxide (CO) test.

          -  Willing and able to comply with study instructions and commit to all follow-up visits,
             and willing and able to abide by all study requirements and restrictions.

          -  Ability to understand, agree to, and sign the study informed consent form (ICF) prior
             to initiation of any protocol related procedures.

        Exclusion Criteria:

          -  Self-reported substance or alcohol dependence or abuse (excluding nicotine and
             caffeine) within the past 2 years, as defined by the Diagnostic and Statistical Manual
             of Mental Disorders (DSM-IV) and/or subjects who have ever been in a substance or
             alcohol rehabilitation program to treat their substance or alcohol dependence.

          -  History of serious adverse reactions or hypersensitivity to any drug; or known allergy
             to any of the test product(s), or any components in the test product(s); or history of
             hypersensitivity; or allergic reactions to any of the study preparations as described
             in the Investigator's Brochure; or severe allergic reaction (including anaphylaxis) to
             any food, or bee stings or previous status asthmaticus.

          -  History of renal stones or taking cardiac nitrates.

          -  Any clinically significant central nervous system (e.g., seizures), cardiac,
             pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions or history of
             such conditions that, in the opinion of the investigator, may place the subject at an
             unacceptable risk as a participant in this trial or may interfere with the
             distribution, metabolism, or excretion of drugs.

          -  Abnormal physical findings of clinical significance, at screening or on Day -1, which
             would interfere with the objectives of the study.

          -  History or presence of orthostatic hypotension (~20 mmHg drop in systolic blood
             pressure, or ~10 mmHg drop in diastolic blood pressure, or subject experiences
             lightheadedness or dizziness) at screening or on Day-1.

          -  Clinically significant abnormal laboratory values (as determined by the Investigator)
             at the screening evaluation.

          -  Presence or history of allergies requiring acute or chronic treatment (except seasonal
             allergic rhinitis).

          -  12-lead ECG obtained at screening with PR >240 msec, QRS >110 msec, and QTc >440 msec
             for males and >450 msec for females, bradycardia (<50 bpm), or clinically significant
             minor ST wave changes on the screening ECG or any other changes on the screening ECG
             that would interfere with measurement of the QT interval.

          -  Major surgical interventions within 6 months before the study.

          -  Has a positive pre-study hepatitis B surface antigen; positive hepatitis C virus (HCV)
             antibody or detectable HCV ribonucleic acid (RNA); or positive human immunodeficiency
             virus (HIV) antibody result.

          -  Use of a prohibited medication or supplement, as specified in Section 9.6.

          -  Has a history of regular alcohol consumption averaging >14 drinks/week for men and >9
             drinks/week for women (1 drink (10 g alcohol] = 100 ml of wine or 280 ml of standard
             strength beer or 30 ml of 80 proof distilled spirits) within 6 months of the screening
             visit.

          -  Loss of 500 ml, or more, of blood during the 3-month period before the drug
             administration, e.g., blood donor.

          -  Symptoms of a significant somatic or mental illness in the 4-week period preceding
             drug administration, as per investigator discretion.

          -  Exclude subjects with a positive breath alcohol test or urine drug screen at
             screening. Suspected false positive results may be repeated at the discretion of the
             Investigator.

          -  Concurrent participation in another drug or device research study or within 30 days of
             participation in another drug or device research study.

          -  Considered by the Investigator to be an unsuitable candidate for this study.

          -  Women who are breastfeeding, pregnant, or intend to become pregnant during the course
             of the study.

          -  An employee of the sponsor or research site personnel directly affiliated with this
             study or their immediate family members defined as a spouse, parent, child, or
             sibling, whether biological or legally adopted.
      

Gender

All

Ages

18 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Treva Tyson, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02259595

Organization ID

HPN-07-PK-101


Responsible Party

Sponsor

Study Sponsor

Otologic Pharmaceutics, Inc.


Study Sponsor

Treva Tyson, MD, Principal Investigator, Wake Research Associates


Verification Date

April 2015