R-PrEP: Time to Protection and Adherence Requirements of Raltegravir With or Without Lamivudine in Protection From HIV Infection

• Sponsor: Guy's and St Thomas' NHS Foundation Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT03205566
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 2
• Actual Duration (Months): 12.2
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

This study evaluates whether a 7-day course of Raltegravir 400mg bd or Raltegravir 400mg/lamivudine 150mg bd can prevent HIV from infecting genital tissue and will relate the level of drug in the blood to the level of drug in genital tissue and to the ability to of HIV to infect genital tissue. As well as determining whether these regimes can provide ex vivo protection against HIV, this study will also determine speed to provision of protection and a 48 hour PK/PD decay profile of Raltegravir following drug cessation after attaining steady state concentrations. The results will also inform all future HIV pre-exposure prophylaxis studies of Raltegravir and form the basis for large scale clinical trials without the need for tissue sampling. To date, efficacy studies assessing PrEP regimens have utilized HIV-acquisition endpoints with the consequence being such studies are required to be large in subject number in order to power observations. In addition the study will provide for the first time data on HIV protection rather than just Raltegravir drug levels in tissue, and allow assessment of the possibility of Raltegravir being used as an intermittent dosing regimen in PrEP.

Condition or Disease	Intervention/Treatment	Phase
Hiv	Drug: Raltegravir 400Mg Tab; Drug: Lamivudine 150Mg Tablet	Phase 4

Detailed Description

This is a multi-site, open-label, randomised, pharmacokinetic (PK) and pharmacodynamic (PD) trial whereby 36 individuals (18 women and 18 men) will be randomised according to gender 1:1:1:1:1:1 to one of 6 arms (A 1 A 2 A 3 B 1 B 2 B 3). The result being 3 women and 3 men will be in each arm. The letter dictates the ART regimen order and the number dictates the time points that tissue sampling will occur on and off ART. Two ART regimes will be investigated and all individuals will receive both regimes separated by a one month wash out.

Arm A (A 1 A 2 A 3): will start with 7 days Raltegravir 400mg bd and then have a one month wash out before then starting 7 days Raltegravir 400mg /lamivudine 150mg bd.

Arm B (B 1 B 2 B 3): will start with 7 days Raltegravir 400mg /lamivudine 150mg bd and then have a one month wash out before then starting 7 days Raltegravir 400mg bd. This will remove sequential selection bias. All individuals will receive tissue sampling at baseline for ex vivo analysis to ensure biopsies are infectable on challenge assays. Sampling from women will avoid menstruation and if possible focus on the luteal phase of the menstrual cycle. Individuals will receive another set of tissue sampling during and after ART in phase 1, have a 4 week wash out period and then have another set of sampling during and after ART in phase 2. Individuals will therefore have 5 sets of sampling during the trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: The Time to Protection and Adherence Requirements of Raltegravir With or Without Lamivudine in Protection From HIV Infection
• Actual Study Start Date: Sep 19, 2017
• Actual Primary Completion Date: Sep 24, 2018
• Actual Study Completion Date: Sep 24, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A Raltegravir, then Raltegravir/Lamivudine 7 days Raltegravir 400mg bd followed by minimum 4 weeks wash out and then 7 days Raltegravir 400mg/lamivudine 150mg (oral tablets) bd.	Drug: Raltegravir 400Mg Tab; bd for 7 days; Other Names: Isentress ; Drug: Lamivudine 150Mg Tablet; + Raltegravir 400Mg tablet bd for 7 days; Other Names: Epivir
Active Comparator: Arm B Raltegravir/Lamivudine, then Raltegravir Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days followed by a minimum of 4 weeks wash out and then 7 days Raltegravir 400mg bd.	Drug: Raltegravir 400Mg Tab; bd for 7 days; Other Names: Isentress ; Drug: Lamivudine 150Mg Tablet; + Raltegravir 400Mg tablet bd for 7 days; Other Names: Epivir

Outcome Measures

Primary Outcome Measures

1. The Level of Raltegravir Alone or Raltegravir /Lamivudine Required in the Plasma, Vagina and Rectum for 100% ex Vivo Protection From HIV [Through Study completion, an average of 55 days]

   The level of Raltegravir alone or Raltegravir /lamivudine required in the plasma, vagina and rectum for 100% ex vivo protection from HIV . High viral dose challenge: ex vivo challenge of tissue with 104 TCID50/mL HIV-1BaL Low viral dose challenge: ex vivo challenge of tissue with 102 TCID50/mL HIV-1BaL

Secondary Outcome Measures

1. The Time From First Dose of Drug to Maximum Mucosal ex Vivo Protection From HIV. [Up to 7 days from first dose]

   Time in days from first receipt of antiretroviral (Raltegravir 400mg +/-lamivudine) until maximal ex vivo protection (against high or low titre of HIV-1BaL) was observed.

2. Number of Adverse Events Based on PE, Blood Test and Event Reporting on Raltegravir Based PrEP, in HIV Negative Individuals [Through Study completion, an average of 55 days]

   Subject safety and tolerability will be determined by physical examination, blood tests and adverse event reporting. FBC, U&E and LFTs will be carried out at baseline and thereafter as symptom directed. Adverse event review. If significant adverse events have been reported, these will be clinically followed in accordance to the instruction of the study physician.

3. The Time to Cessation of Mucosal ex Vivo Protection From HIV After Stopping ART at Steady State. [5 days post last dose]

   Time in days from stopping antiretroviral (Raltegravir 400mg +/-lamivudine) until ex vivo protection (against high or low viral titre of HIV-1BaL) was no longer observed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. The ability to understand and sign a written informed consent form prior to participation in any screening procedures and must be willing to comply with all trial requirements.

2. Male or non-pregnant, non-lactating females

3. Age between 18 to 60 years, inclusive.

4. Body Mass Index (BMI) of 16 to 35 kg/m2, inclusive.

5. Negative antibody/antigen combined test for HIV.

6. Absence of any significant health problems (in the opinion of the investigator) on the basis of the screening procedures; including medical history, physical examination, vital signs.

7. Women participating in sexual intercourse that could result in pregnancy -must use an adequate form of contraception throughout the study and for two weeks after the study. This includes intrauterine device, condoms, anatomical sterility in self or partner. Oral hormonal methods and implant contraceptives are allowed but only in combination with the additional protection of a barrier method.

8. Female participants may not use any vaginal products or objects or have vaginal sex for 48 hours before and after the collection of vaginal fluid and vaginal biopsies. This list includes tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method),douches, lubricants, vibrators/dildos, and drying agents.

9. Males participating in sexual intercourse that could result in pregnancy must use condoms during the duration of the study.

10. Men and women cannot use anal products or objects including but not exclusive to douches, lubricants and vibrators/dildos, butt plugs or urethral sounds or have receptive anal intercourse for 48 hours before and after the collection of rectal biopsies.

11. Willing to abstain from multivitamins and antacids for the study duration.

Exclusion Criteria:

1. Any significant acute or chronic medical illness.

2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs or clinical laboratory determinations.

3. Positive blood screen for syphilis, hepatitis B (HBs Ag) and/or C antibodies.

4. Positive blood screen for HIV antibodies.

5. Positive screen for sexually transmitted infections at screening visit

6. High-risk behaviour for HIV infection which is defined as having one of the following within three months before trial day 0 (first dose): had unprotected vaginal or anal sex with a known HIV infected person or a casual partner. engaged in sex work for money or drugs. acquired a bacterial sexually transmitted disease in the past 3 months. having a known HIV positive partner either currently or in the previous six months Females who are pregnant or breast-feeding.

7. Clinically significant laboratory abnormalities (according to normal range as defined by central laboratory).

8. Participation in a clinical trial of an Investigational product within 1 month of planned baseline enrolment in this study.

9. Ingestion of H2 receptor antagonists or proton pump inhibitor drugs in the preceding 14 days

10. Current of planned use of anti-epileptics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Harrison Wing, Guy's Hospital	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Guy's and St Thomas' NHS Foundation Trust

Investigators

• Study Director: Julie Fox, Guy's and St Thomas' NHS Foundation Trust

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 23, 2018

More Information

Publications

• Anton PA, Saunders T, Elliott J, Khanukhova E, Dennis R, Adler A, Cortina G, Tanner K, Boscardin J, Cumberland WG, Zhou Y, Ventuneac A, Carballo-Diéguez A, Rabe L, McCormick T, Gabelnick H, Mauck C, McGowan I. First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy. PLoS One. 2011;6(9):e23243. doi: 10.1371/journal.pone.0023243. Epub 2011 Sep 28.
• García-Lerma JG, Otten RA, Qari SH, Jackson E, Cong ME, Masciotra S, Luo W, Kim C, Adams DR, Monsour M, Lipscomb J, Johnson JA, Delinsky D, Schinazi RF, Janssen R, Folks TM, Heneine W. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med. 2008 Feb;5(2):e28. doi: 10.1371/journal.pmed.0050028.
• Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapía M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernández T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallás EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587-99. doi: 10.1056/NEJMoa1011205. Epub 2010 Nov 23.
• Herrera C, Cranage M, McGowan I, Anton P, Shattock RJ. Colorectal microbicide design: triple combinations of reverse transcriptase inhibitors are optimal against HIV-1 in tissue explants. AIDS. 2011 Oct 23;25(16):1971-9. doi: 10.1097/QAD.0b013e32834b3629.
• O'Quigley J, Zohar S. Experimental designs for phase I and phase I/II dose-finding studies. Br J Cancer. 2006 Mar 13;94(5):609-13. Review.

• Responsible Party: Guy's and St Thomas' NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT03205566
• Other Study ID Numbers: 202316
• First Posted: Jul 2, 2017
• Last Update Posted: Mar 16, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: HIV Infections; Lamivudine; Raltegravir Potassium

Study Results

Participant Flow

Recruitment Details	Potential participants were identified via study poster, internal recruitment emails, and via a list of individuals who had consented to be contacted for further research. Potential participants would contact the team, trial discussed & information sheet provided. If still interested, would be consented and screening visit booked.
Pre-assignment Detail	Once participants were consented to the study, they undertook a screening visits to confirm eligibility. If eligibility was not confirmed, the participant was deemed a screen failure and not randomised to the trial.

Arm/Group Title	Raltegravir, Then Raltegravir/Lamivudine	Raltegravir Lamivudine, Then Raltegravir
Arm/Group Description	Raltegravir 400mg tablet, taken twice a day for 7days. Washout minimum of 28 days Raltegravir 400mg plus lamivudine 150mg taken twice a day for 7 days	Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Washout minimum 28 days Raltegravir 400Mg Tab: bd for 7 days
Period Title: Phase 1
STARTED	19	19
COMPLETED	18	18
NOT COMPLETED	1	1
Period Title: Phase 1
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Raltegravir, Then Raltegravir Plus Lamivudine	Raltegravir Lamivudine, Then Raltegravir	Total
Arm/Group Description	Raltegravir 400mg tablet, taken twice a day for 7days. Washout period 28 days Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days.	Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Washout period 28 days Raltegravir 400Mg Tab: bd for 7 days	Total of all reporting groups
Overall Participants	19	19	38
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 100%	19 100%	38 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.9 (6.5)	30.9 (8.0)	29 (7.5)
Sex: Female, Male (Count of Participants)
Female	10 52.6%	10 52.6%	20 52.6%
Male	9 47.4%	9 47.4%	18 47.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 15.8%	5 26.3%	8 21.1%
White	16 84.2%	10 52.6%	26 68.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	4 21.1%	4 10.5%
Region of Enrollment (Count of Participants)
United Kingdom	19 100%	19 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	The Level of Raltegravir Alone or Raltegravir /Lamivudine Required in the Plasma, Vagina and Rectum for 100% ex Vivo Protection From HIV
Description	The level of Raltegravir alone or Raltegravir /lamivudine required in the plasma, vagina and rectum for 100% ex vivo protection from HIV . High viral dose challenge: ex vivo challenge of tissue with 104 TCID50/mL HIV-1BaL Low viral dose challenge: ex vivo challenge of tissue with 102 TCID50/mL HIV-1BaL
Time Frame	Through Study completion, an average of 55 days

Outcome Measure Data

Analysis Population Description

Excludes two participants who were withdrawn from the study due to not meeting study inclusion criteria, but who were nonetheless included in safety analyses as they received at least one dose of study medication

Arm/Group Title	Raltegravir	Raltegravir During Combination Treatment	Lamivudine During Combination Treatment
Arm/Group Description	Raltegravir 400mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days	Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days Lamivudine 150Mg Tablet: + Raltegravir 400Mg tablet bd for 7 days	Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days Lamivudine 150Mg Tablet: + Raltegravir 400Mg tablet bd for 7 days
Measure Participants	36	36	36
Plasma: High Dose Challenge in rectal tissue	NA (NA)	669.90 (231.40)	265.10 (76.50)
Plasma: Low viral dose challenge in rectal tissue	979.8 (306.5)	669.90 (231.40)	265.10 (76.50)
Rectal: high viral dose challenge in rectal tissue	NA (NA)	862.35 (237.60)	1722.02 (235.10)
Rectal: Low viral dose challenge in rectal tissue	729.36 (218.10)	862.35 (237.60)	1722.02 (235.10)
Plasma: high viral dose challenge in vaginal tissu	NA (NA)	828.60 (510.30)	266.40 (101.60)
Plasma: low viral dose challenge in vaginal tissue	979.8 (306.5)	281.60 (99.10)	169.10 (19.30)
Plasma: high dose in vaginal tissue	NA (NA)	648.24 (432.90)	1557.80 (206.30)
Plasma: low dose in vaginal tissue	607.60 (157.28)	273.02 (88.40)	1437.80 (133.30)

2. Secondary Outcome

Title	The Time From First Dose of Drug to Maximum Mucosal ex Vivo Protection From HIV.
Description	Time in days from first receipt of antiretroviral (Raltegravir 400mg +/-lamivudine) until maximal ex vivo protection (against high or low titre of HIV-1BaL) was observed.
Time Frame	Up to 7 days from first dose

Outcome Measure Data

Analysis Population Description

Excludes two participants who were withdrawn from the study due to not meeting study inclusion criteria, but who were nonetheless included in safety analyses as they received at least one dose of study medication

Arm/Group Title	Raltegravir	Raltegravir Lamivudine
Arm/Group Description	Raltegravir 400mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days	Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days Lamivudine 150Mg Tablet: + Raltegravir 400Mg tablet bd for 7 days
Measure Participants	36	36
Time from first dose of drug to maximum rectal ex vivo protection from high titer HIV infection	3 (0.58)	2 (0)
Time from first dose of drug to maximum rectal ex vivo protection from low titer HIV infection	2 (0)	2 (0)
Time from first dose of drug to maximum rectal ex vivo protection from High titer HIV infection	2.67 (0.67)	3 (0.68)
Time from first dose of drug to maximum vaginal ex vivo protection from low titer HIV infection	3 (0.45)	3.67 (0.61)

3. Secondary Outcome

Title	Number of Adverse Events Based on PE, Blood Test and Event Reporting on Raltegravir Based PrEP, in HIV Negative Individuals
Description	Subject safety and tolerability will be determined by physical examination, blood tests and adverse event reporting. FBC, U&E and LFTs will be carried out at baseline and thereafter as symptom directed. Adverse event review. If significant adverse events have been reported, these will be clinically followed in accordance to the instruction of the study physician.
Time Frame	Through Study completion, an average of 55 days

Outcome Measure Data

Analysis Population Description

Includes two participants who were withdrawn from the study due to not meeting study inclusion criteria, but who were nonetheless included in safety analyses as they received at least one dose of study medication

Arm/Group Title	Arm A Raltegravir	Arm B Raltegravir Lamivudine
Arm/Group Description	Raltegravir 400mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days	Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days Lamivudine 150Mg Tablet: + Raltegravir 400Mg tablet bd for 7 days
Measure Participants	38	38
Number [Adverse event]	12	15

4. Secondary Outcome

Title	The Time to Cessation of Mucosal ex Vivo Protection From HIV After Stopping ART at Steady State.
Description	Time in days from stopping antiretroviral (Raltegravir 400mg +/-lamivudine) until ex vivo protection (against high or low viral titre of HIV-1BaL) was no longer observed.
Time Frame	5 days post last dose

Outcome Measure Data

Analysis Population Description

Excludes two participants who were withdrawn from the study due to not meeting study inclusion criteria, but who were nonetheless included in safety analyses as they received at least one dose of study medication

Arm/Group Title	Raltegravir	Raltegravir Lamivudine
Arm/Group Description	Raltegravir 400mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days	Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days Lamivudine 150Mg Tablet: + Raltegravir 400Mg tablet bd for 7 days
Measure Participants	36	36
Time to cessation of rectal ex vivo protection from high HIV dose challenge post ART at steady state	3.33 (0.69)	NA (NA)
Time to cessation of rectal ex vivo protection from low HIV dose challenge post ART at steady state	NA (NA)	NA (NA)
Time to cessation of vaginal ex vivo protection from high HIVdose challenge post ART at steady state	4 (1.13)	NA (NA)
Time to cessation of vaginal ex vivo protection from low HIV dose challenge post ART at steady state	5 (1.26)	NA (NA)

Adverse Events

Time Frame	Adverse event data was collected for the duration each subject participated in the trial, this being from enrollment to final visit, which is approximately 55 days.
Adverse Event Reporting Description	All adverse event data that was captured as part of trial participation, including that of individuals withdrawn from the trial, were used in analysis
Arm/Group Title	Arm A Raltegravir		Arm B Raltegravir Lamivudine
Arm/Group Description	Raltegravir 400mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days		Raltegravir 400mg + Lamivudine 150mg tablet, taken twice a day for 7days. Raltegravir 400Mg Tab: bd for 7 days Lamivudine 150Mg Tablet: + Raltegravir 400Mg tablet bd for 7 days
All Cause Mortality
	Arm A Raltegravir		Arm B Raltegravir Lamivudine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Serious Adverse Events
	Arm A Raltegravir		Arm B Raltegravir Lamivudine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Arm A Raltegravir		Arm B Raltegravir Lamivudine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/38 (31.6%)		15/38 (39.5%)
Blood and lymphatic system disorders
Abnormal LFTs	1/38 (2.6%)		0/38 (0%)
Neck lump right side	0/38 (0%)		1/38 (2.6%)
Swollen neck glands	1/38 (2.6%)		1/38 (2.6%)
Gastrointestinal disorders
Acid Reflux	0/38 (0%)		1/38 (2.6%)
Diarrhoea	2/38 (5.3%)		3/38 (7.9%)
Impacted tooth	0/38 (0%)		1/38 (2.6%)
Loose Stool	0/38 (0%)		2/38 (5.3%)
Nausea	1/38 (2.6%)		0/38 (0%)
General disorders
Chills	0/38 (0%)		1/38 (2.6%)
Dehydration	1/38 (2.6%)		0/38 (0%)
Fatigue	2/38 (5.3%)		1/38 (2.6%)
Rectal Pain	1/38 (2.6%)		0/38 (0%)
Infections and infestations
Viral illness with abdominal pain, vomiting, nausea, fever	1/38 (2.6%)		0/38 (0%)
Fever	0/38 (0%)		2/38 (5.3%)
Flu	1/38 (2.6%)		0/38 (0%)
Tonsillitis	2/38 (5.3%)		0/38 (0%)
Injury, poisoning and procedural complications
Fluoxetine Overdose	0/38 (0%)		1/38 (2.6%)
Investigations
Rectal Discomfort and PR bleeding	0/38 (0%)		1/38 (2.6%)
Musculoskeletal and connective tissue disorders
Painful left toe	1/38 (2.6%)		1/38 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Perianal lump	1/38 (2.6%)		1/38 (2.6%)
Nervous system disorders
Headache	1/38 (2.6%)		3/38 (7.9%)
Dizziness	0/38 (0%)		1/38 (2.6%)
Light headedness	0/38 (0%)		1/38 (2.6%)
Psychiatric disorders
Insomnia	0/38 (0%)		1/38 (2.6%)
Nightmares and vivid dreams	0/38 (0%)		5/38 (13.2%)
Sleep disturbance	0/38 (0%)		1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Runny nose	4/38 (10.5%)		0/38 (0%)
Cold	2/38 (5.3%)		0/38 (0%)
Cough	1/38 (2.6%)		0/38 (0%)
Nose bleed	0/38 (0%)		1/38 (2.6%)
Sore Throat	2/38 (5.3%)		0/38 (0%)
Skin and subcutaneous tissue disorders
Folliculitis	0/38 (0%)		1/38 (2.6%)
Vascular disorders
Spotting	0/38 (0%)		2/38 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.