HIV InfectionPhase 1NCT01231451
Depot Contraception With and Without Lopinavir/Ritonavir
A Phase 1 study testing DMPA in people with HIV Infection, run by St Stephens Aids Trust at 1 site in United Kingdom.
Trial summary
DMPA (depot medroxyprogesterone acetate or the 'depot' injection) is a widely used contraception. It is popular in woman with HIV as it probably still works when you take HIV drugs. HIV drugs can increase or decrease the level of other drugs (e.g. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- HIV Infection
- What is being tested?
- DMPA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2010to Jun 2011
- 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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedure and must be willing to comply with all study requirements.
- Non-pregnant, non-lactating premenopausal females.
- No current hormonal contraception (short acting methods eg oral contraceptive pills and patches can be removed at screening)
- Regular menstrual periods such that DMPA can be administered between days 1-5 of menstrual cycle
- Between 18 and 45 years, inclusive.
- Documented HIV-1 infection
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- Must be willing to use a barrier method of contraception to avoid pregnancy throughout the study, and for at least 56 days following completion of the study.
- CD4 count > 200 at screening (Note: retesting of screening CD4 count allowed).
- Clinician and patient happy to delay HAART until week 12 of study
- Not currently on HAART and eligible to receive LPV/r and Truvada as determined by their primary HIV care provider in accordance with treatment guidelines
- If history of HAART exposure, no virological failure (prior drug switches allowed if for tolerability/toxicity/convenience of dosing).
- Agrees not to change regimen, outside the study recommendations, from baseline until end of the treatment period unless this is medically indicated as decided by the treating physician
Who cannot join
- Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include any active clinically significant renal, cardiac, hepatic, pulmonary, vascular, metabolic disorders or malignancy.
- Have a body mass index (BMI) >35
- Personal history of venous thromboembolism (VTE) or pulmonary embolism (PE)
- Presence of any current active AIDS defining illness (Category C conditions in the CDC Classification System for HIV 1993) except stable cutaneous Kaposi's Sarcoma
- Osteoporosis or significant risk factors for osteoporosis (alcohol abuse, long-term anticonvulsants/corticosteroids, BMI less than 18, eating disorder, previous low trauma fracture, significant family history osteoporosis)
- Conditions for which DMPA is contra-indicated or risks outweigh benefits:
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- Significant multiple risk factors for arterial cardiovascular disease
- Vascular disease
- Previous or current venous thromboembolism (VTE) or pulmonary embolism (PE)
- Ischaemic heart disease
- Stroke (history of cerebrovascular accident)
- Headaches migraine with aura, at any age
- Unexplained vaginal bleeding
- Gestational trophoblastic neoplasia (GTN) (includes hydatidiform mole, invasive mole, placental site trophoblastic tumour) hCG abnormal
- Breast cancer (past or current) or strong family history
- Diabetes nephropathy/retinopathy/neuropathy
- Other vascular disease or diabetes of >20 years' duration
- Viral hepatitis (active)
- Presence or history of any sever hepatic disease where liver function tests have not returned to normal
- Cirrhosis (decompensated)
- Clinically relevant alcohol or drug use (positive urine drug screen, excluding cannabinoids) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study.
- The use of disallowed concomitant therapy (See section 5.2).
- Previous allergy to any of the constituents of the study pharmaceuticals.
- Exposure to any investigational drug or placebo within 4 weeks of baseline.
- Any HAART exposure within 6 months of screening for this study (ie participants need to be treatment-naïve or on a treatment interruption for 6 months or more).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Pharmacokinetics of Depot Medroxyprogesterone Acetate (DMPA) in the Absence and Presence of Lopinavir/Ritonavir in HIV-1 Infected Women
DMPA (depot medroxyprogesterone acetate or the 'depot' injection) is a widely used contraception. It is popular in woman with HIV as it probably still works when you take HIV drugs. HIV drugs can increase or decrease the level of other drugs (e.g. contraceptives) in your bloodstream which may make them work less well or increase side effects. It is assumed that DMPA can be given with HIV drugs there are no studies proving this.
The purpose of the study is to investigate whether an HIV drug combination containing lopinavir/ritonavir affects DMPA when they are taken at the same time.
Read the detailed description
Lopinavir/ritonavir (LPV/r) is licensed for use in combination with other antiretrovirals for the treatment of HIV infection. Like other agents from the protease inhibitor class, LPV/r inhibits the 3A isoenzyme of the hepatic cytochrome P450 system and may increase the levels of drugs metabolised via this route. However, LPV/r has also been shown in vivo to induce its own metabolism and to increase the biotransformation of some drugs metabolized by P450 enzymes and by glucuronidation.
Women account for an increasing proportion of the HIV epidemic in the UK. The huge reductions in HIV-related mortality and morbidity associated with the use of effective combination antiretroviral therapy have led to a shift in focus to longer term issues, including reproductive health and contraception. The impact of a variety of antiretrovirals on the plasma pharmacokinetics of oral oestrogen and progesterone preparations have been investigated and in general NNRTIs and boosted PIs cause a reduction in levels of both, particularly oral oestrogen preparations. Most package inserts for combined (oestrogen and progestogen) and progestogen-only oral contraceptives recommend that additional contraceptive methods be employed with concomitant use of enzyme-inducing agents.
Injectable contraception provides highly effective contraception without the need for daily pill taking, an important factor to consider for individuals already taking regular medication. Depot medroxyprogesterone acetate (DMPA) is the most frequently prescribed injectable method. DMPA, like other progestogens, is metabolised by the cytochrome P450 system but interaction studies in women on antiretrovirals are limited. A study of 59 women on DMPA contraception plus an unboosted PI (nelfinavir) or an NNRTI (efavirenz or nevirapine) measured DMPA levels and compared them with 16 women on either no therapy or NRTIs only (no potential for drug interaction). DMPA levels were similar in all groups and suppression of ovulation over a 12 week period was also similar in all groups.
Although the high levels of DMPA achieved over the dosing interval make any pharmacokinetic interaction unlikely to be clinically significant, some clinicians advise a reduction in the interval between DMPA injections from 12 to 10 weeks in patients on an NNRTI or boosted PI; there is no clear evidence to support this approach. Although the described study supports normal dosing intervals for women on an NNRTI, the unboosted PI nelfinavir is not recommended as standard of care and the impact of ritonavir-boosted PIs is unclear. The summary of product characteristics for DMPA advises a normal dosing interval even when using a potent enzyme inducers, suggesting no additional intervention is required when prescribing a boosted PI. Formal pharmacokinetic data is crucial to clarify this important area.
- Conditions
- HIV Infection
- Being tested
- DMPA
- Keywords
- HIV Infection
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMPADrug
All subjects will take DMPA
| Study group | Role | What they receive |
|---|---|---|
| All Subjects | Experimental | All Subjects will receive the same intervention Receives: Drug: DMPA |
What is being measured
The primary outcome is the main question the study is designed to answer.
pharmacokinetics of depot medroxyprogesterone acetate (DMPA)
To investigate the pharmacokinetics of depot medroxyprogesterone acetate (DMPA) in the absence and presence of lopinavir/ritonavir in HIV-
1 infected women
Measured: week 1 - week 24
Secondary outcomes (3)
Impact of co-administration of DMPA and lopinavir/ritonavir
To investigate the impact of co-administration of DMPA and lopinavir/ritonavir on surrogate markers of contraceptive efficacy (LH, FSH, oestradiol)
Measured: Week 1 - week 24
Safety of DMPA
To investigate the safety of DMPA in HIV infected women on lopinavir/ritonavir
Measured: Week 1 - week 24
Impact of DMPA on lopinavir/ritonavir plasma concentrations
To investigate the impact of DMPA on lopinavir/ritonavir plasma concentrations compared with historical controls
Measured: week 1 - week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2010 (estimated)
- Study startDec 2010
- Primary completionJun 2011 (estimated)
- Study completionJun 2011 (estimated)
Why it stopped: Ethics board said the study could not be fully justified.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01231451
- Sponsor's protocol ID
- SSAT 038
- Status last verified
- Nov 2010
- First submitted
- 29 Oct 2010
- Last updated
- 29 Nov 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pharmacokinetics of Depot Medroxyprogesterone Acetate (DMPA) in the Absence and Presence of Lopinavir/Ritonavir in HIV-1 Infected Women
- ClinicalTrials.gov ID
- NCT01231451
- Acronym / sponsor ID
- SSAT 038
- Conditions
- HIV Infection
- Keywords
- HIV Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Ethics board said the study could not be fully justified.
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Study start
- Dec 2010
- Primary completion
- Jun 2011 (estimated)
- Study completion
- Jun 2011 (estimated)
- First posted
- 1 Nov 2010 (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.
DMPA (depot medroxyprogesterone acetate or the 'depot' injection) is a widely used contraception. It is popular in woman with HIV as it probably still works when you take HIV drugs. HIV drugs can increase or decrease the level of other drugs (e.g. contraceptives) in your bloodstream which may make them work less well or increase side effects. It is assumed that DMPA can be given with HIV drugs there are no studies proving this.
The purpose of the study is to investigate whether an HIV drug combination containing lopinavir/ritonavir affects DMPA when they are taken at the same time.
Detailed description
Lopinavir/ritonavir (LPV/r) is licensed for use in combination with other antiretrovirals for the treatment of HIV infection. Like other agents from the protease inhibitor class, LPV/r inhibits the 3A isoenzyme of the hepatic cytochrome P450 system and may increase the levels of drugs metabolised via this route. However, LPV/r has also been shown in vivo to induce its own metabolism and to increase the biotransformation of some drugs metabolized by P450 enzymes and by glucuronidation.
Women account for an increasing proportion of the HIV epidemic in the UK. The huge reductions in HIV-related mortality and morbidity associated with the use of effective combination antiretroviral therapy have led to a shift in focus to longer term issues, including reproductive health and contraception. The impact of a variety of antiretrovirals on the plasma pharmacokinetics of oral oestrogen and progesterone preparations have been investigated and in general NNRTIs and boosted PIs cause a reduction in levels of both, particularly oral oestrogen preparations. Most package inserts for combined (oestrogen and progestogen) and progestogen-only oral contraceptives recommend that additional contraceptive methods be employed with concomitant use of enzyme-inducing agents.
Injectable contraception provides highly effective contraception without the need for daily pill taking, an important factor to consider for individuals already taking regular medication. Depot medroxyprogesterone acetate (DMPA) is the most frequently prescribed injectable method. DMPA, like other progestogens, is metabolised by the cytochrome P450 system but interaction studies in women on antiretrovirals are limited. A study of 59 women on DMPA contraception plus an unboosted PI (nelfinavir) or an NNRTI (efavirenz or nevirapine) measured DMPA levels and compared them with 16 women on either no therapy or NRTIs only (no potential for drug interaction). DMPA levels were similar in all groups and suppression of ovulation over a 12 week period was also similar in all groups.
Although the high levels of DMPA achieved over the dosing interval make any pharmacokinetic interaction unlikely to be clinically significant, some clinicians advise a reduction in the interval between DMPA injections from 12 to 10 weeks in patients on an NNRTI or boosted PI; there is no clear evidence to support this approach. Although the described study supports normal dosing intervals for women on an NNRTI, the unboosted PI nelfinavir is not recommended as standard of care and the impact of ritonavir-boosted PIs is unclear. The summary of product characteristics for DMPA advises a normal dosing interval even when using a potent enzyme inducers, suggesting no additional intervention is required when prescribing a boosted PI. Formal pharmacokinetic data is crucial to clarify this important area.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Subjects | Experimental | Drug: DMPAAll Subjects will receive the same intervention |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedure and must be willing to comply with all study requirements.
- Non-pregnant, non-lactating premenopausal females.
- No current hormonal contraception (short acting methods eg oral contraceptive pills and patches can be removed at screening)
- Regular menstrual periods such that DMPA can be administered between days 1-5 of menstrual cycle
- Between 18 and 45 years, inclusive.
Key exclusion criteria (25 listed)
- Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include any active clinically significant renal, cardiac, hepatic, pulmonary, vascular, metabolic disorders or malignancy.
- Have a body mass index (BMI) >35
- Personal history of venous thromboembolism (VTE) or pulmonary embolism (PE)
- Presence of any current active AIDS defining illness (Category C conditions in the CDC Classification System for HIV 1993) except stable cutaneous Kaposi's Sarcoma
- Osteoporosis or significant risk factors for osteoporosis (alcohol abuse, long-term anticonvulsants/corticosteroids, BMI less than 18, eating disorder, previous low trauma fracture, significant family history osteoporosis)
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 |
|---|---|---|
| DMPAAll subjects will take DMPA | Drug | All Subjects |
Primary outcome
pharmacokinetics of depot medroxyprogesterone acetate (DMPA)
Time frame: week 1 - week 24
To investigate the pharmacokinetics of depot medroxyprogesterone acetate (DMPA) in the absence and presence of lopinavir/ritonavir in HIV- 1 infected women
3 secondary outcomes
Impact of co-administration of DMPA and lopinavir/ritonavir
Time frame: Week 1 - week 24
Safety of DMPA
Time frame: Week 1 - week 24
Impact of DMPA on lopinavir/ritonavir plasma concentrations
Time frame: week 1 - week 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2010.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 DMPA in people with HIV Infection, run by St Stephens Aids Trust at 1 site in United Kingdom.
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 12 inclusion and 25 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: withdrawn, as of the sponsor's last update on 29 Nov 2010. 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 Kingdom. 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 was withdrawn before enrolling participants, so there are no results.
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?
pharmacokinetics of depot medroxyprogesterone acetate (DMPA) (time frame: week 1 - week 24). 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 29 Nov 2010; AzTrials last refreshed its copy on 6 Nov 2026.