Clinical trial: Comparison of Concentration-time Course of Plasma and Intracellular Raltegravir in Healthy Volunteers (NCT01027182)

Eligibility criteria:
Inclusion Criteria:

          -  Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2
             and weigh at least 50kg.

          -  Non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for
             at least 3 months prior to selection.

          -  Women of childbearing potential (WOCBP) must not be nursing or pregnant.

          -  Women of childbearing potential (have not been postmenopausal for at least 2 years nor
             undergone total hysterectomy) must have a negative serum Beta-HCG test performed at
             screening.

          -  Female subjects who are not of reproductive potential (have been postmenopausal for at
             least 2 years or undergone total hysterectomy) or whose male partner has undergone
             successful vasectomy with resultant azoospermia or has azoospermia for any other
             reason, are eligible without requiring the use of contraception. Documentation of
             menopause, sterilization (total hysterectomy or vasectomy) and azoospermia must be
             provided to study personnel at time of screening.

          -  Both male and female study volunteers of reproductive potential must agree not to
             participate in a conception process (i.e., active attempt to become pregnant or to
             impregnate via sperm donation or in vitro fertilization), and if participating in
             sexual activity that could lead to pregnancy, the female study volunteer/male partner
             must use a form of contraception as specified below while receiving protocol-specified
             medication(s) and for 7 days after stopping the medication(s). Male study volunteers
             will be required to use a barrier method for at least 7 days after completion of the
             study.

        Exclusion Criteria:

          -  History or current evidence of any significant acute or chronic medical illness that,
             within the investigator's discretion, would interfere with the conduct or
             interpretation of the study.

          -  Proven or suspected acute hepatitis at the time of study entry.

          -  Current or recent (within 3 months) gastrointestinal disease which would interfere
             with the conduct or interpretation of the study.

          -  Any major surgery within 8 weeks of enrollment. Any gastrointestinal surgery that
             could impact upon the absorption of study drug.

          -  Donation of blood or plasma within 60 days of screening.

          -  Inability to tolerate oral medication.

          -  Inability to tolerate venepuncture and/or absence of secure venous access.

          -  Inability to give informed consent voluntarily before the first trial-related
             activity.

          -  Known or suspected HIV infection or chronic HBV or HCV infection

          -  Known active drug or alcohol abuse, which in the opinion of the investigator makes
             study participation to completion unlikely.

          -  Any other significant medical, psychiatric and/or social issue as determined by the
             Investigator that would compromise subject's safety and/or compliance with trial
             procedures.

          -  Subjects with AST, ALT or total bilirubin above the upper limit of normal.

          -  Haemoglobin < 10.9 g/dL, and platelet count < 125,000/mm3.

          -  Creatinine clearance <60 ml/min

          -  Lipase or pancreatic amylase >1.1x ULN

          -  Fasting triglyceride >300 mg/dL.

          -  Absolute Neutrophil Count (ANC) <1300/mm3

          -  Serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range
             [ULN])

          -  Any other clinically significant screening lab abnormality (as determined by the
             investigator)

          -  Exposure to any investigational drug (excluding raltegravir) within 90 days of
             enrollment and throughout the study.

          -  Any previous clinically significant allergy or hypersensitivity or intolerance to
             raltegravir or any other ingredient of the tablets.

          -  Use of any agent, within 2 weeks of dosing, that is known to induce or inhibit drug
             metabolizing enzymes.

          -  Use of concomitant medication, including investigational, prescription, and any
             over-the-counter drugs and dietary supplements with the following exceptions, aspirin,
             acetaminophen, chlorpheniramine, daily multivitamins, mineral supplements and hormonal
             oral contraceptives. Concomitant medication other than those listed above must have
             been discontinued within 14 days of study entry.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 21 Years old.
Subject must be at most 65 Years

Patient description (medical language): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient description (patient's own words): I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Does the patient match the trial criteria? 0