Infection, Human Immunodeficiency VirusPhase 1NCT01498861
Drug Interaction Study Between Dolutegravir and an Oral Contraceptive Containing Norgestimate and Ethinylestradiol
A Phase 1 study testing Ortho-Cyclen and Dolutegravir in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 1 site in United States.
Trial summary
Dolutegravir (DTG, GSK1349572 is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of HIV infection. DTG will likely be used in women on oral contraceptives (OC) for birth control. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infection, Human Immunodeficiency Virus
- What is being tested?
- Ortho-Cyclen and Dolutegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Mar 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin greater than or equal to 1.5 times the upper limit of normal (ULN)
- Healthy female subjects, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied except for ALT, alkaline phosphatase and bilirubin as above may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Female, between 18 and 40 years of age inclusive, at the time of signing the informed consent.
- Women of childbearing potential must use OC Ortho-Cyclen in combination with one of the following appropriate contraceptive methods:a)Complete abstinence from intercourse for at least 14 days prior to the first dose of investigational product (Day 1 of Period 1), throughout the study, and for the subsequent poststudy monitoring or; b) A barrier method plus a spermicide (e.g., condom or diaphragm with spermicidal foam/gel/cream/ suppository for at least 14 days prior to the first dose of investigational product [Day 1 of Period 1]) throughout the study, and for the subsequent poststudy monitoring or; c)Sterilization (vasectomy) of male partner prior to commencement of female subject's last normal menstrual period prior to administration of study drug, and the male partner is the sole partner for that female subject.
- The subject's BMI is 19 to 30 kg/m2 and body weight ≥50 kg (110 lbs) and <114 kg (<250 lbs);
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
- Single QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Who cannot join
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Show all 19Show fewer
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception (see inclusion criteria) from at least 14 days prior to the first dose of investigational product until completion of the follow-up visit;
- Pregnant females as determined by positive hCG test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- History of any condition that would contraindicate OC administration (including hypertension, stroke, ischemic heart disease, venous thromboembolism or family history of thromboembolism, known factor V Leiden mutation or other gene mutations associated with increased risk of thromboembolism, migraine headaches, carcinoma of the breast, liver or endometrium, gallbladder disease, history of undiagnosed abnormal uterine bleeding, etc.).
- If heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
- Unwilling to abstain from tobacco use from the screening visit until the follow-up visit.
- Females with conditions or concurrent medications that could adversely affect hormone levels e.g. oopherectomies and females receiving drug eluting IUDs (e.g. Mirena).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-Blind Study to Evaluate the Pharmacokinetics of an Oral Contraceptive Containing Norgestimate and Ethinyl Estradiol When Co-administered With Dolutegravir in Healthy Adult Female Subjects
Dolutegravir (DTG, GSK1349572 is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of HIV infection. DTG will likely be used in women on oral contraceptives (OC) for birth control. Based on accumulated non-clinical and clinical drug metabolism and pharmacokinetic data, there is a low likelihood of drug interaction between DTG and most widely used OC drugs. The primary objective of this study is to evaluate the effect of DTG administration on the pharmacokinetics and pharmacodynamics of a commonly used oral contraceptive product, Ortho-Cyclen (combination of norgestimate and ethinyl estradiol), in healthy female subjects. Each subject will participate in a Run-in period (if needed), followed by two treatment periods. Approximately 16 subjects will be randomized in a cross-over fashion to either Ortho-Cyclen with DTG or Ortho-Cyclen with Placebo for 10 days and switch to the alternate treatment for another 10 days. Subjects will return to the study center for final follow up evaluations 7 - 14 days after the final dose of study medication.
- Conditions
- Infection, Human Immunodeficiency Virus
- Being tested
- Ortho-Cyclen, Dolutegravir, Placebo
- Medical subject headings
- Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ortho-CyclenDrug
Ortho-cyclen is an oral contraceptive.
DolutegravirDrug
Also called GSK1349572
Dolutegravir is an experimental HIV drug
PlaceboDrug
Placebo is a tablet with no drug in it
| Study group | Role | What they receive |
|---|---|---|
| Run-In Period | Other | Ortho-Cyclen for 21 days. Only for subjects who are not already taking Ortho-Cyclen prior to the study Receives: Drug: Ortho-Cyclen |
| Sequence AB | Experimental | Subjects will take Ortho-Cyclen once a day from Day 1-21 of their menstrual cycle. In addition they will take dolutegravir 50 mg twice a day from Days 1-10 and placebo twice a day from Day 12-21 Receives: Drug: Ortho-Cyclen; Drug: Dolutegravir; Drug: Placebo |
| Sequence BA | Experimental | Subjects will take Ortho-Cyclen once a day from Day 1-21 of their menstrual cycle. In addition they will take placebo twice a day from Days 1-10 and dolutegravir 50 mg twice a day from Day 12-21 Receives: Drug: Ortho-Cyclen; Drug: Dolutegravir; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC(0-tau) of norelgestromin and ethinylestradiol after Ortho-Cyclen alone and after Ortho-Cyclen with dolutegravir
Samples will be collected at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 10 and 21
Measured: Up to 24 hours post-dose
Secondary outcomes (5)
Safety and tolerability of all treatments as assessed by vital signs, AEs, and clinical laboratory tests
Measured: Up to 8 weeks
Composite of norelgestromin pharmacokinetic parameters on Day 10 and Day 21: Cmax, Cmin, tmax, tmin and half life
Samples will be collected at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 10 and 21
Measured: Up to 24 hours post dose
Predose serum levels of luteinizing hormone and follicle stimulating hormone from Periods 1 and 2
Samples will be collected at predose on Days 1, 10, 11, 21 and 22
Measured: predose on Days 1, 10, 11, 21 and 22
Predose serum levels of progesterone from Periods 1 and 2
Samples will be collected at predose on Days 1, 10, 11, 21 and 22
Measured: predose on Days 1, 10, 11, 21 and 22
Composite of dolutegravir pharmacokinetic parameters on Day 10 and Day 21: AUC(0-t), Cmax, tmax, Cmin, C0, Ct and CL/F
Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, and 12 hours post dose on Day 10 and Day 21
Measured: Up to 12 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infection, Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01498861
- Sponsor's protocol ID
- 111855
- Status last verified
- Apr 2012
- First submitted
- 21 Dec 2011
- Last updated
- 21 May 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind Study to Evaluate the Pharmacokinetics of an Oral Contraceptive Containing Norgestimate and Ethinyl Estradiol When Co-administered With Dolutegravir in Healthy Adult Female Subjects
- ClinicalTrials.gov ID
- NCT01498861
- Acronym / sponsor ID
- 111855
- Conditions
- Infection, Human Immunodeficiency Virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Study start
- Dec 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 26 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dolutegravir (DTG, GSK1349572 is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of HIV infection. DTG will likely be used in women on oral contraceptives (OC) for birth control. Based on accumulated non-clinical and clinical drug metabolism and pharmacokinetic data, there is a low likelihood of drug interaction between DTG and most widely used OC drugs. The primary objective of this study is to evaluate the effect of DTG administration on the pharmacokinetics and pharmacodynamics of a commonly used oral contraceptive product, Ortho-Cyclen (combination of norgestimate and ethinyl estradiol), in healthy female subjects. Each subject will participate in a Run-in period (if needed), followed by two treatment periods. Approximately 16 subjects will be randomized in a cross-over fashion to either Ortho-Cyclen with DTG or Ortho-Cyclen with Placebo for 10 days and switch to the alternate treatment for another 10 days. Subjects will return to the study center for final follow up evaluations 7 - 14 days after the final dose of study medication.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Run-In Period | Other | Drug: Ortho-CyclenOrtho-Cyclen for 21 days. Only for subjects who are not already taking Ortho-Cyclen prior to the study |
| Sequence AB | Experimental | Drug: Ortho-Cyclen, Drug: Dolutegravir, Drug: PlaceboSubjects will take Ortho-Cyclen once a day from Day 1-21 of their menstrual cycle. In addition they will take dolutegravir 50 mg twice a day from Days 1-10 and placebo twice a day from Day 12-21 |
| Sequence BA | Experimental | Drug: Ortho-Cyclen, Drug: Dolutegravir, Drug: PlaceboSubjects will take Ortho-Cyclen once a day from Day 1-21 of their menstrual cycle. In addition they will take placebo twice a day from Days 1-10 and dolutegravir 50 mg twice a day from Day 12-21 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin greater than or equal to 1.5 times the upper limit of normal (ULN)
- Healthy female subjects, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied except for ALT, alkaline phosphatase and bilirubin as above may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Female, between 18 and 40 years of age inclusive, at the time of signing the informed consent.
- Women of childbearing potential must use OC Ortho-Cyclen in combination with one of the following appropriate contraceptive methods:a)Complete abstinence from intercourse for at least 14 days prior to the first dose of investigational product (Day 1 of Period 1), throughout the study, and for the subsequent poststudy monitoring or; b) A barrier method plus a spermicide (e.g., condom or diaphragm with spermicidal foam/gel/cream/ suppository for at least 14 days prior to the first dose of investigational product [Day 1 of Period 1]) throughout the study, and for the subsequent poststudy monitoring or; c)Sterilization (vasectomy) of male partner prior to commencement of female subject's last normal menstrual period prior to administration of study drug, and the male partner is the sole partner for that female subject.
- The subject's BMI is 19 to 30 kg/m2 and body weight ≥50 kg (110 lbs) and <114 kg (<250 lbs);
Key exclusion criteria (19 listed)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ortho-CyclenOrtho-cyclen is an oral contraceptive. | Drug | Run-In Period, Sequence AB, Sequence BA |
| DolutegravirAlso: GSK1349572Dolutegravir is an experimental HIV drug | Drug | Sequence AB, Sequence BA |
| PlaceboPlacebo is a tablet with no drug in it | Drug | Sequence AB, Sequence BA |
Primary outcome
AUC(0-tau) of norelgestromin and ethinylestradiol after Ortho-Cyclen alone and after Ortho-Cyclen with dolutegravir
Time frame: Up to 24 hours post-dose
Samples will be collected at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 10 and 21
5 secondary outcomes
Safety and tolerability of all treatments as assessed by vital signs, AEs, and clinical laboratory tests
Time frame: Up to 8 weeks
Composite of norelgestromin pharmacokinetic parameters on Day 10 and Day 21: Cmax, Cmin, tmax, tmin and half life
Time frame: Up to 24 hours post dose
Predose serum levels of luteinizing hormone and follicle stimulating hormone from Periods 1 and 2
Time frame: predose on Days 1, 10, 11, 21 and 22
Predose serum levels of progesterone from Periods 1 and 2
Time frame: predose on Days 1, 10, 11, 21 and 22
Composite of dolutegravir pharmacokinetic parameters on Day 10 and Day 21: AUC(0-t), Cmax, tmax, Cmin, C0, Ct and CL/F
Time frame: Up to 12 hours post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
ViiV Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ortho-Cyclen and Dolutegravir in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC(0-tau) of norelgestromin and ethinylestradiol after Ortho-Cyclen alone and after Ortho-Cyclen with dolutegravir (time frame: Up to 24 hours post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2012.