Clinical trial NCT02245438 (phase 1, status: terminated)
Conditions: healthy
ICD codes: Z76.3, Z76.2
Drugs: tipranavir low dose, tipranavir high dose, ritonavir low dose, ritonavir high dose, norethindrone-ethinyl estradiol
SMILES: [H][C@@](CC)(C1=CC(NS(=O)(=O)C2=NC=C(C=C2)C(F)(F)F)=CC=C1)C1=C(O)C[C@@](CCC)(CCC2=CC=CC=C2)OC1=O, [H][C@@](CC)(C1=CC(NS(=O)(=O)C2=NC=C(C=C2)C(F)(F)F)=CC=C1)C1=C(O)C[C@@](CCC)(CCC2=CC=CC=C2)OC1=O, CC(C)[C@H](NC(=O)N(C)CC1=CSC(=N1)C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)OCC1=CN=CS1)CC1=CC=CC=C1, CC(C)[C@H](NC(=O)N(C)CC1=CSC(=N1)C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)OCC1=CN=CS1)CC1=CC=CC=C1, [H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3
Eligibility criteria:

        Inclusion Criteria:

          1. Female subjects between 18 and 50 years of age inclusive

          2. A Body Mass Index (BMI) between 18 and 29 kg/m2

          3. Signed informed consent prior to trial participation

          4. Ability to swallow numerous large capsules without difficulty

          5. Acceptable laboratory values that indicate adequate baseline organ function are
             required at the time of screening. Laboratory values are considered to be acceptable
             if severity is less than or equal to Grade 1, based on the AIDS Clinical Trials Group
             Grading Scale. All abnormal laboratory values greater than Grade 1 are subject to
             approval by the trial clinical monitor.

          6. Acceptable medical history, physical examination and ECG, and chest X-ray (if not
             conducted within the last 12 months) are required prior to entering the treatment
             phase of the study

          7. Willingness to abstain from alcohol for 48 hours prior to Study Day 0 and abstain from
             alcohol for the duration of the study. In addition, red wine must not have been
             ingested within 5 days prior to Day 0 (Visit 2)

          8. Willingness to abstain from ingesting grapefruit, grapefruit juice, or products
             containing grapefruit juice, within 10 days before Day 0, Visit 2 and for the duration
             of the study

          9. Willingness to abstain from ingesting Seville oranges, garlic supplements, St. John's
             Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee, tea, cola,
             energy drinks, chocolate, etc) within 5 days of Day 0, Visit 2 and for the duration of
             the study

         10. Willingness to abstain from over the counter herbal medications for the duration of
             the study

         11. Reasonable probability for completion of the study

        Exclusion Criteria:

          1. Female subjects who are of reproductive potential who:

               -  Have positive serum beta-human chorionic gonadotropin at Visit 1, or on Day 0 or
                  Day 1

               -  Have not been using a barrier contraceptive method for at least 3 months prior to
                  Visit 3 (Day 1)

               -  Are not willing to use a reliable method of double-barrier contraception (such as
                  diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during
                  the trial and 30 days after completion/termination

               -  Are breast-feeding

          2. Participation in another trial with an investigational medicine within 30 days prior
             to Day 0 (Visit 2)

          3. Use of any medication listed in the protocol within 30 days prior to Day 0 (Visit 2)

          4. Use of any other pharmacological contraceptive (including oral, patch or injectable
             contraceptives) for 1 month prior to study initiation and for the duration of the
             study

          5. Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the
             trial

          6. History of central nervous system (CNS), gastrointestinal, hepatic, or renal disorders
             within the past sixty (60) days. Subjects will be excluded for these disorders greater
             than sixty days if, in the opinion of the investigator, the subject does not qualify
             as a healthy volunteer

          7. History of thrombotic disease

          8. History of migraine headache

          9. Have serological evidence of hepatitis B or C virus

         10. Have serological evidence of exposure to HIV

         11. Recent history of alcohol or substance abuse (within 6 months of study period)

         12. Cigarette smoking (greater than 10 cigarettes per day)

         13. Blood or plasma donations within 30 days prior to Day 0 (Visit 2) or during the trial.

         14. Subjects with a seated systolic blood pressure either <100 mm Hg or >150 mm Hg;
             resting heart rate either <50 beats/min or >90 beats/min. For subjects with a resting
             heart rate below 50, due to a high fitness level, the investigator may discuss
             exclusion with the medical monitor on a case-by-case basis

         15. Subjects with a history of any illness or allergy that, in the opinion of the
             investigator, might confound the results of the study or pose additional risk in
             administering Tipranavir, Ritonavir or NET/EE to the subject

         16. Subjects who have had an acute illness within 2 weeks prior to Day 0 (Visit 2)

         17. Subjects who are currently taking any over-the-counter drug within 7 days prior to Day
             0,(Visit 2) or who are currently taking any prescription drug that, in the opinion of
             the investigator in consultation with the clinical monitor, might interfere with
             either the absorption, distribution or metabolism of the test substances

         18. Known hypersensitivity to TPV, RTV, or NET/EE

         19. Inability to comply with the protocol