Cutoff Assessment for Codeine in Fingerprint Sweat Relative to Oral Fluid, Following Controlled, Oral Administration of Codeine Phosphate Tablets to 40 Healthy Adults

The Intelligent Fingerprinting Drug Testing System The Intelligent Fingerprinting Drug Testing System utilizes three components for the qualitative determination of codeine in human fingerprint sweat. It is for in vitro diagnostic use only and intended for prescription use indoors by trained personnel. The intended use environment is an indoor office, or an office-like setting such as a portable or prefabricated cabin. The Intelligent Fingerprinting Drug Screening Cartridge, a single-use, lateral-flow immunoassay cartridge, is intended for use with Intelligent Fingerprinting DSR-Plus fluorescence reader. Directly following completion of collecting a full set of 10 fingerprints, the DSC-7 Drug Screening Cartridge is placed in the DSR-Plus fluorescence reader. This test provides only a preliminary result.

Negative results from the Drug Screening cartridge do not require any additional analysis. Non-negative results must be confirmed with a more specific chemical method by using the Sample Collection Cartridge to collect an additional fingerprint sweat specimen. A validated, traceable liquid chromatography/tandem mass spectrometry (LC/MS-MS) method is preferred.

Subjects must be healthy male and non-pregnant female subjects between ages 18 and 55, inclusive, at the time of dosing. Subject body mass index (BMI) must be between 18.0 kg/m2 to 32.0 kg/m2, inclusive, and total weight must be at least 60 kg.

Subjects will check into the clinic the evening prior to codeine phosphate dosing, at least 14 hours prior to dosing, and remain confined in house until at least 24 hours after the initial codeine phosphate dose.

The total number of healthy adult subjects (male and non-pregnant females) required for enrollment in this study protocol is 40. The total duration of the study, from check-in through the end of the study will be approximately 3 days. Subjects will be confined for at least 24 hours after the first codeine dose. Both 60 mg codeine phosphate doses will be given orally in tablet form with 100-120 mL of room temperature water, followed by two oral rinses (rinse and spit) of 30-50 mL water each. 50 mg of naltrexone hydrochloride will be given as a single oral dose with approximately 120 mL of room temperature water at approximately 12 hours (±30 min) prior to the first administration of codeine, again with breakfast at one hour prior to the first codeine phosphate administration, and again 12 hours (±30 min) after the first codeine dose. Additional dose(s) of naltrexone hydrochloride (1 x 50 mg) may be administered at the discretion of the Investigator

Sampling comprises 13 time points for each of fingerprint sweat and oral fluid per subject for opiate content. Baseline biological fluid sampling (fingerprint sweat and oral fluid) will occur within 90 minutes prior to the codeine dosage, then subsequently at 0.5 hours, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5, 10.5, 12.5 and 24 hours (±15 min) after the codeine phosphate dose. At each time point, specimens will be collected in the order of fingerprint sweat (screening cartridge), oral fluid, and fingerprint sweat on the Sample Collection Cartridge. A handwash and 15-minute wait (following handwash) will precede both fingerprint sweat specimen collections.

Screening results from both fingerprint sweat specimens and oral fluid will be recorded from instrumentation (DSR-Plus) or visual read (OralTox) within 10 minutes of sampling as either a negative or non-negative result. Quantitative codeine concentrations will be determined for the specimens described above using a validated LC-MS/MS method.

Inclusion criteria

• Informed of the nature of the study, agreed to, and able to read, review, and sign the informed consent document prior to dosing. The informed consent document will be written in English; therefore, the subject must have the ability to read and communicate in English.
• Completed the screening process within 30 days prior to dosing. Subjects screened as a part of an IRB-approved General Screening Protocol at the clinical research site may be included in this study without additional screening procedures provided all the required screening procedures have been performed within 30 days prior to dosing.
• Healthy male and non-pregnant female subjects between ages 18 and 55, inclusive, at the time of dosing.
• Body mass index (BMI) between 18.0 kg/m2 to 32.0 kg/m2, inclusive, and weigh at least 60 kg.
• Judged by the Investigator and/or designee to be in good health as documented by the medical history, physical examination (including but may not be limited to an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems), vital sign assessments along with oxygen saturation, 12-lead electrocardiogram (ECG), clinical laboratory assessments, and by general observations. Any abnormalities or deviations outside the normal ranges for any of clinical testing (laboratory tests, ECG, etc.) can be repeated at the discretion of the Investigator and/or designee and judged to be not clinically significant for study participation. Any abnormalities or deviations outside the normal range for vital signs can be repeated by clinical staff and judged to be not clinically significant for study participation.
• Subjects with glomerular filtration rate (GFR) of greater than or equal to 60.
• Females of childbearing potential must be willing to practice an acceptable form of contraception, and have a negative serum pregnancy test at screening and a negative urine pregnancy test on admission to the treatment phase of the study.
• Males must agree to practice an acceptable form of contraception.

Exclusion criteria

• More than three digits absent from the hands due to congenital or accidental cause(s).
• Reports receiving any investigational drug/product within 30 days prior to dosing.
• Reports any personal history of substance abuse (including drug/alcohol abuse or addiction) or mental illness (e.g. major depression) within one year prior to screening visit.
• Reports any presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, urologic, gastrointestinal, hepatic, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease as determined by the Investigator.
• Presence of any clinically significant results from laboratory tests, vital signs assessments, as judged by the Investigator.
• Demonstrates a reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody.
• Reports a clinically significant illness during the 30 days prior to dosing (as determined by the Investigator).
• Reports a history of allergic response(s) to opiates, naltrexone or related drugs.
• Reports hypersensitivity to bisulfites.
• Reports history of respiratory depression (e.g., sleep apnea).
• Current severe hypotension (i.e., systolic blood pressure <90 mmHg).
• Reports current presence of acute bronchial asthma/ upper airway obstruction.
• If subject reports a history of clinically significant allergies, including food or drug allergies, as judged by the Investigator.
• Reports history/current condition of adrenal insufficiency.
• Reports history/current condition of renal disease.
• Reports a history of smoking within previous six months.
• Report history/current condition of seizures, increased intracranial pressure, brain tumor, head injuries or impaired consciousness.
• Reports known or suspected gastrointestinal obstruction including, paralytic ileus.
• Reports difficulty fasting or consuming standardized meals.
• Demonstrates a positive pregnancy screen (females only).
• If, in the opinion of the Investigator, the subject is not suitable for the study.