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Study of PF614 Compared to OxyContin® in Healthy Volunteers

Information source: Signature Therapeutics
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Healthy

Intervention: PF614 (Drug); Oxycodone extended-release (Drug)

Phase: Phase 1

Status: Not yet recruiting

Sponsored by: Signature Therapeutics

Official(s) and/or principal investigator(s):
William K Schmidt, PhD, Study Director, Affiliation: Signature Therapeutics

Overall contact:
William K Schmidt, PhD, Phone: 650-331-4003, Email: wschmidt@signaturerx.com

Summary

PF614 is an oxycodone prodrug that is designed for extended-release of oxycodone comparable to OxyContin. This Single Ascending Dose (SAD) study is designed to assess the safety and pharmacokinetics (PK) of PF614 in comparison to standard doses of OxyContin.

Clinical Details

Official title: Phase 1, Single-Center, Dose-Escalation and Fixed-Dose Crossover Food Effect Cohort Study to Determine the Safety and Pharmacokinetics of a Single Oral Dose of PF614 in Healthy Subjects Compared to OxyContin

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Safety and tolerability (Number of participants with adverse events)

Secondary outcome:

Pharmacokinetics (Cmax)

Pharmacokinetics (Tmax)

Pharmacokinetics (AUC)

Dose Selection (Identify doses of PF614 with pharmacokinetics comparable to OxyContin)

Food Effect (Ratio of Cmax in Fed vs. Fasted states)

Food Effect (Ratio of AUC in Fed vs. Fasted states)

Prodrug Fragments (plasma concentration)

Detailed description: PART 1 PHARMACOKINETICS (PK): This will be a Phase 1 randomized, single-center, SAD study in 6 cohorts of 8 healthy male and/or female subjects. The study will evaluate the safety and PK of PF614 and the PK of oxycodone at doses sufficient to characterize the extent to which plasma oxycodone is produced and maintained following oral ingestion of PF614. The PK of the prodrug fragments will also be evaluated. There will be a parallel study arm in each cohort dosed that will use oral OxyContin® as an active comparator. Subjects will receive PF614 (n=6) or OxyContin as comparator (n=2) orally in the fasted state. In addition, all subjects in the SAD part will receive naltrexone at 14 hours pre-dose, 2 hours pre-dose and 10 hours post dose to block the effects of oxycodone. The starting dose for administration of PF614 will be 15 mg. The lowest available dose of OxyContin, 10 mg, will be used as the comparator in the first cohort. PK assessments will be conducted after each cohort to compare the oxycodone area under curve (AUC) of PF614 and OxyContin to determine the most appropriate dose for the subsequent cohorts. PART 2 FOOD EFFECT (FE): This will be a Phase 1, open-label, 2 sequence, cross-over study to investigate the effects of food on the PK of PF614. A cohort of up to 12 subjects will undergo two crossover treatment periods, separated by a minimum 7 day washout. Subjects will be randomized to either the fed or fasted condition in the first treatment, and will receive the opposite treatment on their second visit. Subjects in the fed group will receive the standardized FDA-defined high fat high calorie meal 30 minutes prior to scheduled dosing. The dose of PF614 in the crossover cohort will be selected based on PK assessments from the SAD part of the study. The aim will be to select a dose of PF614 that demonstrates comparable AUC to a 20 mg OxyContin dose. This dose of oxycodone is not expected to produce clinically significant respiratory effects. Regardless, a single 50 mg dose of naltrexone will be administered 10 hours post-dose as a safety precaution before the subjects go to sleep. Administration at this time is unlikely to affect the cleavage of PF614 to oxycodone or the absorption profile for oxycodone. PK data from a similar dose in the blocked cohorts from the dose escalation phase of the study will be compared to PK data from this cohort (fasted state) to assess the impact, if any, of naltrexone on the PK of oxycodone from PF614. Subjects in the FE group will be monitored with continuous oximetry to ensure subject safety.

Eligibility

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Males and females, ages 18-50 years (inclusive) in good general health; 2. Body mass index (BMI) between 18. 0 and 32. 0 kg/m2 (inclusive); 3. Minimum weight of 50. 0 kg, inclusive; 4. Subjects must have a negative screen for drugs of abuse, cotinine, alcohol, hepatitis B-surface antigen, hepatitis C antibody and antibodies against HIV 1 and 2; 5. Female subjects must have a negative serum pregnancy test at screening and a negative

pregnancy test on Day - 1;

6. Females of childbearing potential and males and their female partner(s) of childbearing potential must agree to use 2 forms of contraception, 1 of which must be a barrier method, during the study and for 90 days after the last drug administration. Acceptable barrier forms of contraception are condom and diaphragm. Acceptable nonbarrier forms of contraception for this study are a nonhormonal intrauterine device (IUD), oral contraceptives and/or spermicide; 7. Subjects must have normal or no evidence of clinically significant findings in physical examination and 12-lead electrocardiogram (ECG) according to the PI, and normal vital signs (respiratory rate between 10 and 18 breaths per minute, blood pressure between 100-139/50-89 mmHg, heart rate between 40-100 beats per minute, temperature between 96. 44°F and 100. 04°F (between 35. 8°C and 37. 8°C), and oxygen saturation (SpO2) > 97% in the absence of supplemental oxygen; 8. Clinical laboratory values must be within the normal limits as defined by the clinical laboratory, unless the PI decides that out-of-range values are not clinically significant; 9. Subjects must be able to provide meaningful written informed consent; 10. Subjects must be willing and able to follow study instructions and be likely to complete all study requirements. Exclusion Criteria: 1. History of allergy or sensitivity to oxycodone, OxyContin, any other opiate, naltrexone, or naloxone; 2. History of loud snoring or sleep apnea; 3. History of medical problems encountered with opioid therapy; 4. Urinary cotinine levels indicative of smoking or history of regular use of tobacco-containing or nicotine-containing products within 2 months prior to screening; 5. History of alcoholism or drug abuse (prescription or illicit drugs) according to Diagnostic and Statistical Manual IV-Text Revision (DSM IV-TR) criteria; 6. Use of prescription medications within 14 days of study drug administration, except for contraceptive medications used by female subjects; use of over-the-counter (OTC) medications within 7 days prior to study drug administration; 7. Use of any opioid within 30 days prior to screening; 8. Donation of blood within 60 days prior to screening; 9. Donation of plasma, platelets, or white blood cells within 7 days prior to dosing; 10. Acute illness (eg, gastrointestinal illness, infection such as influenza, upper respiratory tract infection, or known inflammatory process) within 7 days of dosing 11. History of gastrointestinal disturbance requiring frequent use of antacid; 12. History of clinically significant gastrointestinal disease and/or surgery which would result in the subject's inability to absorb or metabolize the study drug (eg, gastrectomy, gastric bypass, cholecystectomy); 13. Anticipated need for surgery or hospitalization during the study or follow-up period; 14. Dosing with an investigational drug or participation in an investigation device study within 30 days or five half-lives of first dose of the study drug; 15. Any other condition, that, in the PI's opinion, (i) puts the subject at increased risk, (ii) could confound the study results (iii) may interfere significantly with the subject's participation in the study or (IV) has the potential to limit the subject's ability to complete the study.

Locations and Contacts

William K Schmidt, PhD, Phone: 650-331-4003, Email: wschmidt@signaturerx.com

PRA Health Sciences - Early Development Services, Lenexa, Kansas 66219, United States; Not yet recruiting
Daniel Dickerson, MD, Phone: 801-892-5169, Email: dickersondaniel@prahs.com
Kyle Robison, MS, CCRP, Phone: 913 410 2384, Email: RobisonKyle@prahs.com
Daniel Dickerson, MD, Principal Investigator
Additional Information

Starting date: August 2015
Last updated: May 22, 2015

Page last updated: August 23, 2015

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