HIV PreventionPhase 1NCT01575405
A Study to Compare Three Different Formulations of Tenofovir 1% Gel When Administered Rectally
A Phase 1 study testing Rectal formulation (RF) of tenofovir 1% gel and Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel in people with HIV Prevention, run by Ian McGowan at 2 sites in United States.
Trial summary
This is a double-blinded, randomized, safety, acceptability, pharmacokinetic, and ex vivo efficacy study of three rectally-applied tenofovir-based microbicide formulations. Approximately 18 total evaluable HIV-negative men and women (~9 per site) will be enrolled across two study sites: University of California at Los… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV Prevention
- What is being tested?
- Rectal formulation (RF) of tenofovir 1% gel and Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2013to Nov 2013
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ≥ Age of 18 at screening
- Willing and able to communicate in English
- Willing and able to provide written informed consent to take part in the study
- Willing and able to provide adequate locator information
- Understands and agrees to local sexually transmitted infection (STI) reporting requirements
- HIV-1 uninfected at screening according to the standard DAIDS algorithm in Appendix II
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- Must have been vaccinated for or have natural immunity to Hepatitis B, which will be verified by a positive Hepatitis B surface antibody (HBsAb) test at screening (Note: One re-screen will be allowed for individuals who are non immune to Hepatitis B but undergo vaccination.)
- Availability to return for all study visits, barring unforeseen circumstances
- Willing to abstain from RAI and practices involving insertion of anything in rectum (drug, enema, penis, or sex toy) for 72 hours before and 72 hours after each flexible sigmoidoscopy and study product exposure.
- Must agree to use study provided condoms for the duration of the study
- Must be in general good health
- Must agree not to participate in other concurrent interventional and/or drug trials
- Per participant report at screening, a history of consensual RAI at least once in the last three months.
- In addition to the criteria listed above, female participants must meet the following criteria:
- Willing to abstain from insertion of anything into vagina (drug, douche, penis, or sex toy) other than the swabs/sponges for study related specimen collection for 24 hours before and after each study product exposure
- Post-menopausal or using (or willing to use) an acceptable form of contraception (e.g., intrauterine device (IUD), hormonal contraception, surgical sterilization, or vasectomization of male partner). If the female participant has female partners only, the method of contraception will be noted as a barrier method in the study documentation. Temporary abstinence due to absence of partner(s) for the duration of the study will be acceptable.
Who cannot join
- Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
- At screening: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current CDC guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis, trichomoniasis, Chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis, or symptomatic genital warts requiring treatment. Note that an HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required. (Note: In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after screening visit will be allowed.)
- Per participant report and/or clinical or laboratory diagnosis, anorectal STI within six months prior to the Screening Visit
- At screening:
- Hemoglobin < 10.0 g/dL
- Platelet count less than 100,000/mm3
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- White blood cell count < 2,000 cells/mm3 or > 15,000 cells/mm3
- For females: calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min (140- age in years) x (weight in kg) x (0.85 for female)/72 x (serum creatinine in mg/dL)
- For males: calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140 - age in years) x (weight in kg) x (1 for male)/72 x (serum creatinine in mg/dL)
- Serum creatinine > 1.3× the site laboratory upper limit of normal (ULN)
- Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 2.5× the site laboratory ULN
- +1 glucose or +1 protein on urinalysis (UA)
- History of bleeding problems (verified via prothrombin time (PT)/ International Normalized Ratio (INR) test)
- Positive for Hepatitis B surface antigen (HBsAg)
- History of significant gastrointestinal bleeding in the opinion of the investigator
- Known allergic reaction to methylparaben, propylparaben, sorbic acid, glycerin, glycerol, or tenofovir
- Current known HIV-infected partner(s)
- By participant report at enrollment, history of excessive daily alcohol use (as defined by the CDC as heavy drinking consisting of an average consumption of more than 2 drinks per day for men, and more than 1 drink per day for women), frequent binge drinking or illicit drug use that includes any injection drugs, methamphetamines (crystal meth), heroin, or cocaine including crack cocaine, within the past 12 months
- Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications during the period of study participation:
- Heparin, including Lovenox®
- Warfarin
- Plavix® (clopidogrel bisulfate)
- Rectally administered medications (including over-the-counter products)
- Acyclovir, valacyclovir, famciclovir, and TDF
- >81 mg of aspirin per day AND unwillingness and/or inability to completely stop all use of aspirin or aspirin-containing medications for 3 days before and 3 days after the biopsy collection procedure
- Non-steroidal anti-inflammatory drugs (NSAIDS)
- Any other drugs that are associated with increased likelihood of bleeding following mucosal biopsy
- By participant report at screening, use of systemic immunomodulatory medications, rectally administered medications, rectally administered products (including condoms) containing N-9, or any investigational products within the 4 weeks prior to the Enrollment/Baseline Evaluation Visit and throughout study participation
- History of recurrent urticaria
- Any other condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease
- In addition to the criteria listed above, female participants will be excluded if they meet any of the following criteria:
- Pregnant at the Enrollment/Baseline Visit
- Breastfeeding at screening or intend to breastfeed during study participation per participant report.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UCLA Center for Prevention Research
Los Angeles, California, 90024
Magee/University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: A Randomized, Double Blind Phase 1 Safety, Acceptability, and Pharmacokinetic Study Comparing Three Formulations of Tenofovir 1% Gel Administered Rectally to HIV-1 Seronegative Adults
This is a double-blinded, randomized, safety, acceptability, pharmacokinetic, and ex vivo efficacy study of three rectally-applied tenofovir-based microbicide formulations. Approximately 18 total evaluable HIV-negative men and women (~9 per site) will be enrolled across two study sites: University of California at Los Angeles (UCLA) and Magee-Womens Research Institute (MWRI) at University of Pittsburgh.
Each participant will experience seven rectal exposures to the rectal-specific formulation (RF) and seven rectal exposures to the reduced glycerin vaginal formulation (RGVF) of tenofovir 1% gel, but only one exposure to the vaginal formulation (VF), which will be coupled with six preceding exposures to the Universal HEC Placebo Gel to balance out the VF study stage. Participant accrual will take approximately 6 months and each participant will be on study for approximately 3 months. The total duration of the study will be approximately 1 year.
Read more
The primary objectives of the study are safety, acceptability, and pharmacokinetics, specifically:
- To evaluate the safety of each tenofovir-based microbicide gel formulation when applied rectally
- To evaluate the acceptability of each tenofovir-based microbicide gel formulation when applied rectally
- To compare systemic and compartment pharmacokinetics among the three tenofovir-based microbicide gel formulations when applied rectally
Secondary objective of the study is to evaluate the mucosal immunotoxicity of each tenofovir-based microbicide gel formulation when applied rectally.
And the exploratory objective of the study is to assess the preliminary (ex vivo) efficacy of each tenofovir-based microbicide gel formulation using biopsy explants after each product is applied rectally.
- Conditions
- HIV Prevention
- Being tested
- Rectal formulation (RF) of tenofovir 1% gel, Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel, Universal HEC Placebo Gel Formulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rectal formulation (RF) of tenofovir 1% gelDrug
The RF is a translucent colorless viscous gel formulation containing 1% (w/w) of tenofovir (PMPA) formulated in purified water with EDTA, glycerin, methylparaben, propylparaben, carbopol, sodium carboxy methyl cellulose, and pH adjusted to 7. The RF is close to isoosmolar with an osmolality of 479 mOsmol/kg. Seven doses of this formulation will be used.
Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gelDrug
The original VF is a transparent, viscous gel formulation containing 1% (weight/weight) of tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl]adenine monohydrate), formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben, hydroxyethylcellulose, and pH adjusted to 4-5. One dose of this formulation will be used, with 6 doses of the HEC placebo gel preceding it to balance out this study stage. The reduced glycerin formulation (RGVF) is a modification of the original VF - it has lower glycerin content than the VF and a significantly reduced osmolality (836 or 846 versus 3111 mOsmol/kg). Lowering the glycerin content lowered the viscosity, so the HEC concentration was increased by 10% (a change considered to be insignificant). The amount of parabens was increased by 10% each to improve the antimicrobial effectiveness. The RGVF formulation has since been modified to increase the viscosity. Seven doses of RGVF will be used in this study.
Universal HEC Placebo Gel FormulationDrug
The Universal HEC Placebo Gel contains hydroxyethylcellulose as the gelling agent, purified water, sodium chloride, sorbic acid and sodium hydroxide. The gel is isotonic and formulated at a pH of 4.4 to avoid disrupting the normal vaginal pH and has minimal buffering capacity to avoid the inactivation of sexually transmitted pathogens. Hydroxyethylcellulose is used to approximate the viscosity of microbicide gel candidates. Each pre-filled applicator will deliver approximately 4 mL of HEC placebo gel. Six doses of this gel will be used to balance out the VF stage of the study.
| Study group | Role | What they receive |
|---|---|---|
| Rectal-specific formulation (RF) stage | Experimental | During this stage, participants will receive seven rectally-administered doses of the rectal-specific formulation (RF), with the first and last dose administered in clinic and five doses in between self-administered by a participant at home. Various specimens will be collected after administration of the last dose, including blood, vaginal and rectal fluids, and endoscopic biopsies. Blood and fluids will be additionally collected at 2hr, 4hr, and 24hr post-last-dose administration. Receives: Drug: Rectal formulation (RF) of tenofovir 1% gel |
| Vaginal formulation (VF) stage | Active comparator | During this stage, only one exposure to the vaginal formulation (VF) will be administered (as the seventh dose in the stage), but it will be coupled with six preceding exposures to the Universal HEC Placebo Gel to balance it out against the other three stages in the study.
First and last doses will be administered in clinic, and after the administration of the last dose, various specimens will be collected, including blood, vaginal and rectal fluid, and endoscopic biopsies. Additional blood and fluids will be collected at 2, 4, and 24 hours post seventh dose administration. Receives: Drug: Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel; Drug: Universal HEC Placebo Gel Formulation |
| Reduced Glycerin Vaginal Formulation (RGVF) stage | Active comparator | During this stage, participants will receive seven rectally-administered doses of the reduced glycerin vaginal formulation (RGVF), with the first and last dose administered in clinic and five doses in between self-administered by a participant at home. Various specimens will be collected after administration of the last dose, including blood, vaginal and rectal fluids, and endoscopic biopsies. Blood and fluids will be additionally collected at 2hr, 4hr, and 24hr post-last-dose administration. Receives: Drug: Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of adverse events and/or abnormal laboratory values Grade 2 or higher
Grade 2 or higher clinical and laboratory adverse events as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 and Addenda 1 and 3 (Female Genital and Rectal Grading Tables for Use in Microbicide Studies) will be used to assess safety.
Measured: Participants will be followed for the duration of study, an expected average of 12 weeks
Proportion of participants reporting product characteristics as barriers in use
We will calculate the proportion of participants who report product characteristics to be considered a barrier in use, operationalized as having a rating of lower than 3 on a 5-point Likert scale, in disliking or likelihood of future barrier in use. The phone interviews will be audio-taped, transcribed, and analyzed for content. In this process, we will be able to integrate the qualitative data to gain insights about the quantitative responses.
Measured: 24 hours post seventh dose administration of each study product
Area Under Curve (AUC)
Tenofovir concentrations will be measured via:
- Plasma
- PBMC (intracellular)
- Rectal fluid
- Vaginal fluid, in female participants
- Rectal mucosal tissue homogenates
- Rectal MMC
Tenofovir diphosphate concentrations will be measured via:
- PBMC
- Rectal mucosal tissue homogenates
- Rectal MMC
Measured: 30 min, 2hr, 4hr, and 24hr post-dose at Visits 4, 5, 7, 8, 10, and 11
Secondary outcomes (5)
Changes in rectal microflora
Microflora measures will be graded on a 0 to 4 ordinal scale and recorded at baseline and post-exposure. Depending on the empirical distributions across the points in this scale, statistical procedures will either involve analysis of the actual pre-post differences (ordinal) or dichotomized versions of the pre and post scores (binary).
Measured: 30 min before first dose and 24 hr after seventh dose of each study gel
Changes in cytokine levels in rectal secretions
Comparisons will be used to examine whether (i) there is an overall change in cytokine levels before/after (24 hours) each product exposure and (ii) whether the study products differ significantly from each other in pre-post change.
Measured: 30 min before first dose, 30 min before seventh dose, and 24 hr after seventh dose of each study gel
Changes in rectal histology
Examination of two point (normal versus abnormal) or three point (normal, slightly abnormal, abnormal) scales will be undertaken. As above, comparisons will be used to examine whether (i) there is an overall change in histology scores before/after (24 hours) each product exposure and (ii) whether the study products differ significantly from each other in pre-post change.
Measured: 30 min post seventh dose of each study gel
Changes in rectal tissue CD4 cell phenotype
comparisons will be used to examine whether (i) there is an overall change in cell populations before/after (24 hours) each product exposure and (ii) whether the study products differ significantly from each other in pre-post change.
Measured: 30 min post seventh dose of each study gel
Changes in intestinal mucosal cytokine mRNA levels
mRNA levels will be used to evaluate stability (intra-subject correlations) and clinically meaningful differences between treatment groups.
Measured: 30 min post administration of seventh dose each study gel
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2012 (estimated)
- Study startMar 2013
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV PreventionStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ian McGowan
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), CONRAD
- Responsible party
- Sponsor-investigator, Ian McGowan, University of Pittsburgh
- Investigators
- Ian McGowan, MD, PhD, FRCP, Study chair, Magee-Women's Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01575405
- Sponsor's protocol ID
- CHARM-01
- Other IDs
- 5U19AI082637
- Status last verified
- Nov 2013
- First submitted
- 29 Feb 2012
- Last updated
- 7 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mcgowan I, Cranston RD, Duffill K, Siegel A, Engstrom JC, Nikiforov A, Jacobson C, Rehman KK, Elliott J, Khanukhova E, Abebe K, Mauck C, Spiegel HM, Dezzutti CS, Rohan LC, Marzinke MA, Hiruy H, Hendrix CW, Richardson-Harman N, Anton PA. A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study). PLoS One. 2015 May 5;10(5):e0125363. doi: 10.1371/journal.pone.0125363. eCollection 2015.
PubMed 25942472
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind Phase 1 Safety, Acceptability, and Pharmacokinetic Study Comparing Three Formulations of Tenofovir 1% Gel Administered Rectally to HIV-1 Seronegative Adults
- ClinicalTrials.gov ID
- NCT01575405
- Acronym / sponsor ID
- CHARM-01
- Conditions
- HIV Prevention
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Ian McGowanUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), CONRAD
- Study start
- Mar 2013
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 11 Apr 2012 (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.
This is a double-blinded, randomized, safety, acceptability, pharmacokinetic, and ex vivo efficacy study of three rectally-applied tenofovir-based microbicide formulations. Approximately 18 total evaluable HIV-negative men and women (~9 per site) will be enrolled across two study sites: University of California at Los Angeles (UCLA) and Magee-Womens Research Institute (MWRI) at University of Pittsburgh.
Each participant will experience seven rectal exposures to the rectal-specific formulation (RF) and seven rectal exposures to the reduced glycerin vaginal formulation (RGVF) of tenofovir 1% gel, but only one exposure to the vaginal formulation (VF), which will be coupled with six preceding exposures to the Universal HEC Placebo Gel to balance out the VF study stage. Participant accrual will take approximately 6 months and each participant will be on study for approximately 3 months. The total duration of the study will be approximately 1 year.
The primary objectives of the study are safety, acceptability, and pharmacokinetics, specifically:
- To evaluate the safety of each tenofovir-based microbicide gel formulation when applied rectally
- To evaluate the acceptability of each tenofovir-based microbicide gel formulation when applied rectally
- To compare systemic and compartment pharmacokinetics among the three tenofovir-based microbicide gel formulations when applied rectally
Secondary objective of the study is to evaluate the mucosal immunotoxicity of each tenofovir-based microbicide gel formulation when applied rectally.
And the exploratory objective of the study is to assess the preliminary (ex vivo) efficacy of each tenofovir-based microbicide gel formulation using biopsy explants after each product is applied rectally.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rectal-specific formulation (RF) stage | Experimental | Drug: Rectal formulation (RF) of tenofovir 1% gelDuring this stage, participants will receive seven rectally-administered doses of the rectal-specific formulation (RF), with the first and last dose administered in clinic and five doses in between self-administered by a participant at home. Various specimens will be collected after administration of the last dose, including blood, vaginal and rectal fluids, and endoscopic biopsies. Blood and fluids will be additionally collected at 2hr, 4hr, and 24hr post-last-dose administration. |
| Vaginal formulation (VF) stage | Active comparator | Drug: Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel, Drug: Universal HEC Placebo Gel FormulationDuring this stage, only one exposure to the vaginal formulation (VF) will be administered (as the seventh dose in the stage), but it will be coupled with six preceding exposures to the Universal HEC Placebo Gel to balance it out against the other three stages in the study. First and last doses will be administered in clinic, and after the administration of the last dose, various specimens will be collected, including blood, vaginal and rectal fluid, and endoscopic biopsies. Additional blood and fluids will be collected at 2, 4, and 24 hours post seventh dose administration. |
| Reduced Glycerin Vaginal Formulation (RGVF) stage | Active comparator | Drug: Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gelDuring this stage, participants will receive seven rectally-administered doses of the reduced glycerin vaginal formulation (RGVF), with the first and last dose administered in clinic and five doses in between self-administered by a participant at home. Various specimens will be collected after administration of the last dose, including blood, vaginal and rectal fluids, and endoscopic biopsies. Blood and fluids will be additionally collected at 2hr, 4hr, and 24hr post-last-dose administration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- ≥ Age of 18 at screening
- Willing and able to communicate in English
- Willing and able to provide written informed consent to take part in the study
- Willing and able to provide adequate locator information
- Understands and agrees to local sexually transmitted infection (STI) reporting requirements
Key exclusion criteria (33 listed)
- Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
- At screening: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current CDC guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis, trichomoniasis, Chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis, or symptomatic genital warts requiring treatment. Note that an HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required. (Note: In cases of non-anorectal GC/CT identified at screening, one re-screening 2 months after screening visit will be allowed.)
- Per participant report and/or clinical or laboratory diagnosis, anorectal STI within six months prior to the Screening Visit
- At screening:
- History of significant gastrointestinal bleeding in the opinion of the investigator
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 |
|---|---|---|
| Rectal formulation (RF) of tenofovir 1% gelThe RF is a translucent colorless viscous gel formulation containing 1% (w/w) of tenofovir (PMPA) formulated in purified water with EDTA, glycerin, methylparaben, propylparaben, carbopol, sodium carboxy methyl cellulose, and pH adjusted to 7. The RF is close to isoosmolar with an osmolality of 479 mOsmol/kg. Seven doses of this formulation will be used. | Drug | Rectal-specific formulation (RF) stage |
| Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gelThe original VF is a transparent, viscous gel formulation containing 1% (weight/weight) of tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl]adenine monohydrate), formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben, hydroxyethylcellulose, and pH adjusted to 4-5. One dose of this formulation will be used, with 6 doses of the HEC placebo gel preceding it to balance out this study stage. The reduced glycerin formulation (RGVF) is a modification of the original VF - it has lower glycerin content than the VF and a significantly reduced osmolality (836 or 846 versus 3111 mOsmol/kg). Lowering the glycerin content lowered the viscosity, so the HEC concentration was increased by 10% (a change considered to be insignificant). The amount of parabens was increased by 10% each to improve the antimicrobial effectiveness. The RGVF formulation has since been modified to increase the viscosity. Seven doses of RGVF will be used in this study. | Drug | Reduced Glycerin Vaginal Formulation (RGVF) stage, Vaginal formulation (VF) stage |
| Universal HEC Placebo Gel FormulationThe Universal HEC Placebo Gel contains hydroxyethylcellulose as the gelling agent, purified water, sodium chloride, sorbic acid and sodium hydroxide. The gel is isotonic and formulated at a pH of 4.4 to avoid disrupting the normal vaginal pH and has minimal buffering capacity to avoid the inactivation of sexually transmitted pathogens. Hydroxyethylcellulose is used to approximate the viscosity of microbicide gel candidates. Each pre-filled applicator will deliver approximately 4 mL of HEC placebo gel. Six doses of this gel will be used to balance out the VF stage of the study. | Drug | Vaginal formulation (VF) stage |
Primary outcome
Occurrence of adverse events and/or abnormal laboratory values Grade 2 or higher
Time frame: Participants will be followed for the duration of study, an expected average of 12 weeks
Grade 2 or higher clinical and laboratory adverse events as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 and Addenda 1 and 3 (Female Genital and Rectal Grading Tables for Use in Microbicide Studies) will be used to assess safety.
Proportion of participants reporting product characteristics as barriers in use
Time frame: 24 hours post seventh dose administration of each study product
We will calculate the proportion of participants who report product characteristics to be considered a barrier in use, operationalized as having a rating of lower than 3 on a 5-point Likert scale, in disliking or likelihood of future barrier in use. The phone interviews will be audio-taped, transcribed, and analyzed for content. In this process, we will be able to integrate the qualitative data to gain insights about the quantitative responses.
Area Under Curve (AUC)
Time frame: 30 min, 2hr, 4hr, and 24hr post-dose at Visits 4, 5, 7, 8, 10, and 11
Tenofovir concentrations will be measured via: * Plasma * PBMC (intracellular) * Rectal fluid * Vaginal fluid, in female participants * Rectal mucosal tissue homogenates * Rectal MMC Tenofovir diphosphate concentrations will be measured via: * PBMC * Rectal mucosal tissue homogenates * Rectal MMC
5 secondary outcomes
Changes in rectal microflora
Time frame: 30 min before first dose and 24 hr after seventh dose of each study gel
Changes in cytokine levels in rectal secretions
Time frame: 30 min before first dose, 30 min before seventh dose, and 24 hr after seventh dose of each study gel
Changes in rectal histology
Time frame: 30 min post seventh dose of each study gel
Changes in rectal tissue CD4 cell phenotype
Time frame: 30 min post seventh dose of each study gel
Changes in intestinal mucosal cytokine mRNA levels
Time frame: 30 min post administration of seventh dose each study gel
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 7 Nov 2013.
- Derived from this study: PubMed 25942472Mcgowan I, Cranston RD, Duffill K, Siegel A, Engstrom JC, Nikiforov A, Jacobson C, Rehman KK, Elliott J, Khanukhova E, Abebe K, Mauck C, Spiegel HM, Dezzutti CS, Rohan LC, Marzinke MA, Hiruy H, Hendrix CW, Richardson-Harman N, Anton PA. A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study). PLoS One. 2015 May 5;10(5):e0125363. doi: 10.1371/journal.pone.0125363. eCollection 2015.
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HIV Infections
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.
Ian McGowan, MD, PhD, FRCP study chair
Magee-Women's Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rectal formulation (RF) of tenofovir 1% gel and Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel in people with HIV Prevention, run by Ian McGowan at 2 sites 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 16 inclusion and 33 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 7 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Occurrence of adverse events and/or abnormal laboratory values Grade 2 or higher (time frame: Participants will be followed for the duration of study, an expected average of 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01575405, which also lists 1 linked publication.
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 7 Nov 2013.