First in Humans Study of JDTic
First in Humans Study of JDTic
This is the first study to be conducted in humans for JDTic, a new chemical entity, with
 evaluations focusing on the safety, tolerability, and pharmacokinetics (PK) of JDTic
 following administration of single oral doses. JDTic is a novel, selective κ opioid receptor
 antagonist and is currently being developed by RTI International as a potential
 pharmacotherapy to treat cocaine dependence. This study has the possibility of identifying
 the maximum tolerated dose in humans and a surrogate measure of JDTic pharmacodynamic (PD)
 activity. Data from this study will be used to plan for and define dose ranges for subsequent
 studies, as well as to identify potential indicators of JDTic pharmacological activity.
JDTic-001 will be a single-center, double-blind, placebo-controlled, single-dose study
 evaluating three planned escalating oral doses of JDTic in three planned cohorts of healthy
 male subjects without a history of illicit drug use within the 12 months preceding the
 Screening Visit, or other substances of abuse within the 12 months preceding the Screening
 Visit. Each cohort of up to 8 eligible subjects will be enrolled sequentially to receive a
 single oral dose of study drug under fasting conditions. JDTic dose escalation will occur
 only if safety and PK data permit. A semi adaptive dosing plan will be followed such that the
 first two dose cohorts will comprise 4 subjects each and the third planned cohort will
 comprise 8 subjects. If adverse events (AEs) considered to be at least possibly related to
 study medication by the Clinic Principal Investigator are noted in study subjects
 participating in the first two cohorts, an additional 4 subjects will be dosed at the same
 dose level as part of the affected cohort, unless otherwise determined by the Safety Review
 Team (SRT) as guided by the JDTic-001 Data and Safety Monitoring Plan (DSMP). Should dosing
 of additional subjects occur in the first cohort of subjects, then the second cohort of
 subjects will also include 8 subjects. In each cohort, subjects will be randomized 3:1 active
 drug: placebo in a double-blind fashion.

 The planned JDTic dose levels to be evaluated are 1 mg, 3 mg, and 10 mg; however, the actual
 dose levels evaluated may be different, and/or additional dose levels may be added by
 protocol amendment, depending on the safety and PK results of the lower doses.

 Subjects will be admitted to the clinic the day before dosing and will be confined to the
 clinic for 6 nights, with safety and PK evaluations and assessments lasting approximately 125
 hours following administration of study drug. Subjects will be required to remain confined to
 the clinic for more than 6 nights if they experience persistent AEs that require observation
 and/or the Clinic Principal Investigator or qualified designee (physician who is listed as a
 subinvestigator on FDA Form 1572) considers it unsafe to release the subject from the clinic.
 Additionally, alternate subjects admitted with Group 1 but not dosed may remain in the clinic
 overnight for the possibility of being dosed with Group 2 and therefore would spend more than
 6 nights in the clinic. Subjects will return to the clinic at 14 days after receiving their
 dose for a follow-up visit. If, at this visit, changes in the POMS™ assessment are noted that
 are considered significant in the Clinic Principal Investigator's opinion, or if a subject
 has an ongoing AE, the subject will return to the clinic every 14 days (or sooner, if
 clinically indicated) from the date of the follow-up visit until these changes/AEs have
 resolved. Subject participation in the study will last up to 4 weeks, from screening through
 the follow-up visit, depending on the date the subject's screening visit begins with respect
 to the date he is dosed, and provided no additional follow-up visits are necessary.
Inclusion Criteria:

 1. Subject provides signed and dated, written informed consent before any study-specific
 procedures are performed, including washout of any medications. Subjects will be asked
 to meet the food, beverage and physical activity restrictions required for the
 screening visit prior to signing consent.

 2. Subject is a healthy adult male aged 18 to 50 years, inclusive, at the time of
 consent.

 3. Subject has a body weight of at least 50 kg and a body mass index (BMI) in the range
 of 18 to 30

 4. Subject has a negative prestudy urine drug screen and no history of use of illicit
 drugs within 12 months of the screening visit or other substances of abuse within 12
 months of the screening visit.

 5. Subject has not used tobacco for at least 90 days prior to screening.

 6. Subject has no history of any cardiovascular disease and no clinically significant ECG
 results at screening.

 7. Subject is negative for hepatitis C (HCV) antibodies, hepatitis B (HBV) surface
 antigen, and human immunodeficiency virus (HIV) at screening.

 8. Subject is in good general health in the opinion of the Clinic Principal Investigator
 and as determined by medical history, physical examination, orthostatic vital signs
 (supine, sitting, and standing blood pressure and heart rate; supine respiratory rate
 and oral temperature), 12-lead ECG, and clinical laboratory tests at screening.
 Additionally, the subject's clinical laboratory test results must meet the following
 criteria:

 - Within normal limits: Reticulocyte count

 - Within upper limit of normal and not clinically significantly below the lower limit
 of normal: Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Gamma
 glutamyl transferase (GGT) Prothrombin time (PT) Activated partial thromboplastin time
 (aPTT) Serum troponin I Blood urea nitrogen (BUN) Creatinine Bilirubin, total Alkaline
 phosphatase Creatine kinase Lactate dehydrogenase (LDH)

 - No clinically significant abnormalities: Sodium Protein, total Calcium Chloride
 Phosphorus Albumin Globulin Cholesterol Triglycerides Red blood cells (RBC) White
 blood cells (WBC) Hematocrit Hemoglobin Platelets Glucose Potassium WBC differential
 RBC indices Uric acid Urinalysis

 9. Subject is willing to use barrier contraception with spermicide during sexual
 intercourse and is also willing to not donate sperm while enrolled in this study and
 for at least 90 days after receiving his dose of study drug.

 10. Subject is willing and able to comply with study instructions and restrictions and is
 available to complete the study assessments as required by the protocol

 11. Subject is fluent in English.

 Exclusion Criteria:

 1. Subject has a history or evidence of hepatic, GI, renal, respiratory, ophthalmic,
 cardiovascular, hematologic, endocrine/metabolic, neurologic, immunologic, oncologic,
 or psychiatric illness or significant abnormalities; OR other condition(s)/surgical
 intervention(s) known to interfere with the absorption, distribution, metabolism, or
 excretion of drugs.

 2. Subject has a clinically significant abnormal ECG at screening or prior to dosing.
 Multiple premature atrial contractions or multiple premature ventricular contractions
 (PVCs), with the exception of non-clinically significant unifocal PVCs, are considered
 clinically significant, as are bundle branch blocks, second or third degree heart
 block, or any arrhythmia other than respiratory sinus arrhythmia.

 3. Subject has one or more ECG parameters outside the following ranges at Screening or
 just prior to dosing:

 Heart rate less than 55 or greater than 100 beats per minute (bpm), PR interval less
 than 120 or greater than 180 msec, QRS duration less than 70 or greater than 100 msec,
 QT interval (Bazett) greater than 420 msec

 4. One or more of the Subject's supine vital signs are outside the ranges specified
 below:

 -  Systolic blood pressure: 90-140 mmHg, inclusive

 -  Diastolic blood pressure: 60-90 mmHg, inclusive

 -  Heart rate: 55-100 beats per minute (bpm), inclusive

 -  Respiratory rate: 12-20 breaths per minute, inclusive

 -  Oral temperature: 97.0-99.7 degrees Fahrenheit, inclusive

 5. Subject has a history or current evidence of early cardiac repolarization.

 6. Subject has a history or family history of QT prolongation, arrhythmia, or
 uncontrolled hypertension.

 7. Subject has a history of seizure, head injury, neurosurgery or brain trauma, or a
 family history of nontraumatic seizure.

 8. Subject has an infection of any type or clinically significant abnormality identified
 by the screening medical or laboratory evaluations.

 9. Subject has consumed alcohol within 48 hours prior to the screening visit or is
 unwilling to discontinue alcohol consumption within 48 hours of being admitted to the
 clinic.

 10. Subject has a history of significant alcohol consumption, defined as an average weekly
 intake of greater than 21 units or an average daily intake of greater than 3 units,
 with 1 unit equivalent to 1 can or bottle (12 oz) of beer, or 1 measure (1.5 oz) of
 spirits, or 1 glass (5 oz) of wine.

 11. Subject is unwilling to discontinue the consumption of caffeine containing beverages
 72 hours prior to clinic admission.

 12. Subject has consumed or is unwilling to abstain from consuming grapefruit or
 grapefruit-, poppy seed-, or quinine-containing substances, within 14 days of clinic
 admission.

 13. Subject has used a prescription medication within 30 days prior to receiving his dose
 of study medication; or has used nonprescription medications, dietary supplements, or
 herbal supplements within 14 days of receiving his dose of study medication, with the
 exception of acetaminophen, which may be taken up to 24 hours prior to dosing.

 14. Subject has had any acute GI illness or infection within 14 days prior to receiving
 his dose of study medication.

 15. Subject has participated in an investigational trial within 45 days prior to receiving
 his first dose of study medication.

 16. Subject is unable to donate blood, has a clotting disorder(s), or has donated blood or
 lost a significant amount of blood within 8 weeks prior to screening.

 17. Subject has an unexplained weight loss or gain (greater than 10 percent) within 30
 days prior to screening.

 18. Subject has an allergy to or has experienced side effects with opioid antagonists

 19. Subject is unable to respond to or recognize potential side effects of the study drug.
 This may include, but is not limited to, subjects with a mental illness or disorder.

 20. Subject has any condition or set of circumstances not otherwise excluded that in the
 judgment of the Clinic Principal Investigator could interfere with the subject's
 ability to comply with the protocol requirements and restrictions and completion of
 study evaluations, or could pose safety risks to the subject.

 21. Subject has performed strenuous exercise within 48 hours prior to the screening
 examination or refuses to abstain from strenuous exercise from the date of consent
 provision until the completion of the follow-up visit.