Evaluating the Safety, Tolerability, and Pharmacokinetics of an Investigational, Injectable HIV Medicine (GSK1265744) in HIV-Uninfected Adults
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT02178800
Collaborator
(none)
199
8
2
41.3
24.9
0.6
Study Details
Study Description
Brief Summary
This study will evaluate the safety, tolerability, and pharmacokinetics (which is how the body interacts with drugs) of an investigational, injectable HIV medicine (GSK1265744) in healthy, HIV-uninfected adults.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This study will evaluate GSK1265744, which is an investigational, injectable HIV medicine. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of GSK1265744 in healthy, HIV-uninfected adults.
This study will enroll two cohorts of participants (Cohort 1 and Cohort 2). Within each cohort, participants will be randomly assigned to one of two groups: Group 1 will receive GSK1265744 tablets (also called oral 744) and injections (also called GSK1265744 long acting or 744LA), and Group 2 will receive placebo tablets and injections. Participants in Cohort 1 will attend several study visits through Week 81 or Week 105. Participants in Cohort 2 will attend several study visits through Week 85 or Week 109. From study entry through Week 4, participants in both cohorts will take a GSK1265744 tablet (Group 1) or a placebo tablet (Group 2) once a day. For 1 week after participants stop taking their assigned tablets, study researchers will assess safety and tolerability. If no safety or tolerability concerns are identified, participants will enter the injection phase of the study. Participants in Cohort 1 will receive two injections of GSK1265744 (Group 1) or placebo (Group 2) at Weeks 5, 17, and 29. Participants in Cohort 2 will receive one injection of GSK1265744 (Group 1) or placebo (Group 2) at Weeks 5, 9, 17, 25, and 33.
All study visits will include HIV counseling, a physical examination, a medical history review, and a blood collection. Select study visits will include adherence counseling, central nervous system (CNS) symptom assessment, behavioral and acceptability assessments, a urine collection, an electrocardiogram (ECG), and rectal and/or vaginal swabs.
Study Design
Study Type:
Interventional
Actual Enrollment
:
199 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase IIa Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the Investigational Injectable HIV Integrase Inhibitor, GSK1265744, in HIV-uninfected Men and Women
Study Start Date
:
Feb 1, 2015
Actual Primary Completion Date
:
Apr 5, 2017
Actual Study Completion Date
:
Jul 13, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 1: GSK1265744 Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. |
Drug: GSK1265744 Tablets
30-mg tablets, taken orally
Other Names:
Drug: Injectable GSK1265744
Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections
Cohort 2: 600-mg injection, administered as one IM gluteal injection
Other Names:
|
| Placebo Comparator: Group 2: Placebo Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. |
Drug: Placebo for GSK1265744 Tablets
Taken orally
Drug: Injectable Placebo for GSK1265744
Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections
Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Experiencing Any Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities That Occur From the Initial Injection to Week 41 Among Participants Who Receive at Least One Injection (Injectable Phase Only) [Measured through Week 41]
An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm.
- Number of Participants Who Discontinue Injectable Study Product for Reasons of Toxicity, Tolerability, or Acceptability That Occur From the Initial Injection to Week 41 Among Participants Who Receive at Least One Injection (Injectable Phase Only) [Measured through Week 41]
Stratified by arm
- Plasma Drug Levels of GSK1265744 at Designated Time Points After Each Injection of 744LA (Injectable Formulation of GSK1265744) [Measured through Week 41]
Geometric means and 90% prediction intervals by sex at birth and cohort are reported.
Secondary Outcome Measures
- Number of Participants Experiencing Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities During Tail Phase [Measured from 12 weeks after last injection through Week 105 for Cohort 1 and 8 weeks after last injection through Week 109 for Cohort 2]
An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm.
- Number of Participants Experiencing Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities Prior to Completion of the Oral Phase [Measured through Week 5]
An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm.
- Number of Participants Willing to Use an Injectable Agent Such as the Study Product for HIV Prevention in the Future [Measured from week 6 through Week 30 in cohort 1 and Week 34 in cohort 2]
Stratified by Visit and Cohort
- Number of Participants With HIV Infections Through the Study Period, Stratified by Arm [Measured through Week 105 for Cohort 1 and Week 109 for Cohort 2]
- Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period [Measured through Week 77]
Week 29/31 is a combination of week 29, cohort 1 and week 33, cohort 2. The outcome in this table is stratified by arm.
- Number of Injectable Hormonal-contraception-using Female Participants Experiencing Grade 2 or Higher Clinical AE and Laboratory Abnormalities During Oral Phase [Measured through Week 4]
An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm.
- Number of Injectable Hormonal-contraception-using Female Participants Experiencing Grade 2 or Higher Clinical AE and Laboratory Abnormalities During Injection Phase [Measured from first injection through 12 weeks after last injection for Cohort 1 and 8 weeks after last injection for Cohort 2]
- Number of Injectable Hormonal-contraception-using Female Participants Who Discontinue Study Product for Reasons of Toxicity, Tolerability, or Acceptability During Oral Phase [Measured through Week 4]
Stratified by arm
- Number of Injectable Hormonal-contraception-using Female Participants Who Discontinue Study Product for Reasons of Toxicity, Tolerability, or Acceptability During Injection Phase [Measured from first injection through 12 weeks after last injection for Cohort 1 and 8 weeks after last injection for Cohort 2]
- Number of Participants Who Discontinue Oral Study Product for Reasons of Toxicity, Tolerability, or Acceptability Prior to Completion of the Oral Phase [Measured through Week 4]
Stratified by arm
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Men and women, 18 to 65 years old at the time of screening
-
Willing to provide informed consent for the study
-
In the last 12 months (at the time of screening):
-
No self-reported unprotected anal or vaginal intercourse with someone known to be HIV-infected or of unknown HIV infection status
-
No self-reported stimulant use (cocaine [including crack], methamphetamine, or non-physician-prescribed pharmaceutical-grade stimulants) or inhaled nitrate
-
No self-reported illicit injection drug use of any kind
-
No self-reported diagnosis of gonorrhea (GC), chlamydia (CT), incident syphilis, bacterial vaginosis, or trichomoniasis
-
Not reporting five or more different sexual partners, regardless of use of protection or knowledge of HIV status. More information on this criterion is available in the protocol.
-
In general good health, as evidenced by the following laboratory values, which must be from specimens obtained within 45 days prior to study enrollment:
-
Non-reactive/negative HIV test results. More information on this criterion is available in the protocol.
-
Hemoglobin greater than 11 g/dL
-
Absolute neutrophil count greater than 750 cells/mm^3
-
Platelet count greater than or equal to 100,000/mm^3
-
Calculated creatinine clearance greater than or equal to 70 mL/minute using the Cockcroft-Gault equation
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to the upper limit of normal (ULN)
-
Total bilirubin less than or equal to Grade 1 and direct bilirubin less than or equal to ULN
-
Hepatitis B surface antigen (HBsAg) negative
-
Hepatitis C Ab negative
-
Note: Chemistry and hematology parameters which do not meet the inclusion criteria above may be repeated once during screening.
-
No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records). More information on this criterion is available in the protocol.
-
No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
-
Willing to undergo all required study procedures
Additional requirements for all women:
-
If of reproductive potential (defined as pre-menopausal women who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy), must have a negative urine pregnancy test performed (and results known) within 48 hours before initiating the protocol-specified medication(s) at enrollment. Women are considered menopausal if they have not had a menses for at least 12 months and have a follicle stimulating hormone (FSH) level of greater than 40 IU/L; if FSH testing is not available, they must have had amenorrhea for 24 or more consecutive months. (FSH testing is not a protocol requirement.)
-
If of reproductive potential and participating in sexual activity that could lead to pregnancy, women must agree to use a form of contraception during the trial and for 30 days after stopping the oral study medication or for 52 weeks after stopping the long acting injectable from the list below:
-
Intrauterine device (IUD) or intrauterine system (IUS) that meets less than 1% failure rate as stated in the product label
-
Hormone-based contraceptive
Exclusion Criteria:
-
One or more reactive or positive HIV test result at Screening or Enrollment, even if HIV infection is not confirmed
-
Any active sexually transmitted infection detected by laboratory testing at Screening
-
Co-enrollment in any other HIV interventional research study or other concurrent studies which may interfere with this study (as provided by self-report or other available documentation; exceptions may be made if appropriate after consultation with the Clinical Management Committee [CMC].)
-
Past or current participation in HIV vaccine trial. An exception will be made for participants that can provide documentation of receipt of placebo (not active arm).
-
Use of antiretroviral therapy (ART) (e.g., for non-occupational post-exposure prophylaxis [PEP] or PrEP) in the 90 days prior to study entry
-
Clinically significant cardiovascular disease, including:
-
ECG (one repeat ECG is allowed during screening; may be performed on the same day) with:
-
heart rate less than 45 or greater than 100 beats per minute for men, and less than 50 or greater than 100 beats per minute for women
-
interval from the beginning of the Q wave to the end of the S wave (QRS) duration greater than 120 msec
-
corrected QT (QTc) interval (B or F) greater than 450 msec
-
evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes) (except early repolarization)
-
any clinically significant conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular [AV] block [2nd degree (type II) or higher], Wolf Parkinson White [WPW] syndrome) (any question of clinical significance should be referred to the CMC for adjudication)
-
sinus pauses greater than 3 seconds
-
any clinically significant arrhythmia that, in the opinion of the Investigator of Record (IoR) or designee, will interfere with the safety for the individual participant (any question of clinical significance should be referred to the CMC for adjudication)
-
or history of non-sustained (greater than or equal to 3 consecutive ventricular ectopic beats on ECG at screening or entry) or sustained ventricular tachycardia
-
History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease
-
Systolic blood pressure at screening outside the range of 90 to 140 mm Hg or diastolic blood pressure outside the range of 45 to 90 mm Hg (confirmed on repeat measurement)
-
Underlying skin disease or currently active skin disorder (e.g., infection, inflammation, dermatitis, eczema, psoriasis, urticaria). Mild cases of localized acne or folliculitis or other mild skin condition may not be exclusionary at the discretion of the IoR or designee in consultation with the CMC.
-
Has a tattoo or other dermatological condition overlying the buttock region that in the opinion of the IoR or designee, in consultation with the CMC, may interfere with interpretation of injection site reactions
-
Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy)
-
Coagulopathy (primary or iatrogenic) that would contraindicate IM injection (concomitant anticoagulant or anti-platelet therapy use should be discussed with the CMC)
-
Active or planned use of prohibited medications as described in the Investigator's Brochure or listed in the Study Specific Procedures (SSP) Manual (provided by self-report, or obtained from medical history or medical records)
-
A score of greater than or equal to 8 on the WHO Alcohol Use Disorders Identification Test (AUDIT) at screening. Note: A score of greater than or equal to 8 indicates a medium to high level of problem alcohol use.
-
For women: pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study
-
A history of seizure disorder, by self-report
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA CARE Center CRS | Los Angeles | California | United States | 90035 |
| 2 | Bridge HIV CRS | San Francisco | California | United States | 94143 |
| 3 | George Washington Univ. CRS | Washington | District of Columbia | United States | 20006 |
| 4 | Chapel Hill CRS | Chapel Hill | North Carolina | United States | 27599 |
| 5 | Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS | Rio de Janeiro | Brazil | 21040-360 | |
| 6 | Malawi CRS | Lilongwe | Malawi | ||
| 7 | Soweto HPTN CRS | Johannesburg | Gauteng | South Africa | 1862 |
| 8 | Vulindlela CRS | Durban | KwaZulu-Natal | South Africa | 4013 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Raphael J. Landovitz, MD, MSc, University of California, Los Angeles
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02178800
Other Study ID Numbers:
- HPTN 077
- 11964
First Posted:
Jul 1, 2014
Last Update Posted:
Oct 18, 2021
Last Verified:
Oct 1, 2021
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Period Title: Overall Study | ||
| STARTED | 151 | 48 |
| COMPLETED | 131 | 42 |
| NOT COMPLETED | 20 | 6 |
Baseline Characteristics
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection | Total of all reporting groups |
| Overall Participants | 151 | 48 | 199 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
33
(11.4)
|
35
(11.0)
|
33
(11.3)
|
| Age, Customized (Count of Participants) | |||
| 18 - 25 |
52
34.4%
|
9
18.8%
|
61
30.7%
|
| 26 - 35 |
53
35.1%
|
17
35.4%
|
70
35.2%
|
| 36 - 45 |
21
13.9%
|
14
29.2%
|
35
17.6%
|
| 46 - 55 |
15
9.9%
|
4
8.3%
|
19
9.5%
|
| 56 - 65 |
10
6.6%
|
4
8.3%
|
14
7%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
100
66.2%
|
32
66.7%
|
132
66.3%
|
| Male |
51
33.8%
|
16
33.3%
|
67
33.7%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Latino |
36
23.8%
|
11
22.9%
|
47
23.6%
|
| Non-hispanic Asian |
3
2%
|
2
4.2%
|
5
2.5%
|
| Non-hispanic Black |
64
42.4%
|
18
37.5%
|
82
41.2%
|
| Non-hispanic White |
42
27.8%
|
12
25%
|
54
27.1%
|
| Non-hispanic mixed/other |
6
4%
|
5
10.4%
|
11
5.5%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
80
53%
|
26
54.2%
|
106
53.3%
|
| Malawi |
14
9.3%
|
3
6.3%
|
17
8.5%
|
| Brazil |
24
15.9%
|
10
20.8%
|
34
17.1%
|
| South Africa |
33
21.9%
|
9
18.8%
|
42
21.1%
|
Outcome Measures
| Title | Number of Participants Experiencing Any Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities That Occur From the Initial Injection to Week 41 Among Participants Who Receive at Least One Injection (Injectable Phase Only) |
|---|---|
| Description | An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm. |
| Time Frame | Measured through Week 41 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes participants who receive at least one injection in the study. |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 134 | 43 |
| Count of Participants [Participants] |
121
80.1%
|
38
79.2%
|
| Title | Number of Participants Who Discontinue Injectable Study Product for Reasons of Toxicity, Tolerability, or Acceptability That Occur From the Initial Injection to Week 41 Among Participants Who Receive at Least One Injection (Injectable Phase Only) |
|---|---|
| Description | Stratified by arm |
| Time Frame | Measured through Week 41 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes participants who received at least one injection in the study. |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 134 | 43 |
| Count of Participants [Participants] |
11
7.3%
|
2
4.2%
|
| Title | Plasma Drug Levels of GSK1265744 at Designated Time Points After Each Injection of 744LA (Injectable Formulation of GSK1265744) |
|---|---|
| Description | Geometric means and 90% prediction intervals by sex at birth and cohort are reported. |
| Time Frame | Measured through Week 41 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK sample size varies by visit due to reasons such as missing visits, different schedule and sample contamination. |
| Arm/Group Title | Female, Cohort 1 | Male, Cohort 1 | Female, Cohort 2 | Male, Cohort 2 |
|---|---|---|---|---|
| Arm/Group Description | Female, GSK1265744 arm, Cohort 1 participants who received at least one injection only. Plasma drug concentrations at Week 6, 9,13,17,18,23,29,30,35 and 41 are measured. | Male, GSK1265744 arm, Cohort 1 participants who received at least one injection only. Plasma drug concentrations at Week 6, 9,13,17,18,23,29,30,35 and 41 are measured. | Female, GSK1265744 arm, Cohort 2 participants who received at least one injection only. Plasma drug concentrations at Week 6, 9,10,13,17,18,21,25,26,29,33,34,37 and 41 are measured. | Male, GSK1265744 arm, Cohort 2 participants who received at least one injection only. Plasma drug concentrations at Week 6, 9,10,13,17,18,21,25,26,29,33,34,37 and 41 are measured. |
| Measure Participants | 49 | 25 | 40 | 20 |
| Week 6 |
1.32
|
2.40
|
1.29
|
2.28
|
| Week 9 |
1.49
|
1.77
|
1.31
|
1.79
|
| Week 10 |
2.56
|
3.58
|
||
| Week 13 |
1.18
|
0.90
|
2.24
|
2.55
|
| Week 17 |
0.95
|
0.49
|
1.82
|
1.29
|
| Week 18 |
2.11
|
2.33
|
3.09
|
2.73
|
| Week 21 |
2.74
|
2.07
|
||
| Week 23 |
2.02
|
1.48
|
||
| Week 25 |
2.00
|
1.11
|
||
| Week 26 |
3.07
|
2.84
|
||
| Week 29 |
1.37
|
0.78
|
2.68
|
2.17
|
| Week 30 |
2.78
|
3.48
|
||
| Week 33 |
2.10
|
1.50
|
||
| Week 34 |
3.59
|
3.60
|
||
| Week 35 |
2.41
|
1.85
|
||
| Week 37 |
2.73
|
2.71
|
||
| Week 41 |
1.68
|
0.82
|
2.06
|
1.68
|
| Title | Number of Participants Experiencing Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities During Tail Phase |
|---|---|
| Description | An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm. |
| Time Frame | Measured from 12 weeks after last injection through Week 105 for Cohort 1 and 8 weeks after last injection through Week 109 for Cohort 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This includes participants who entered tail phase |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 130 | 42 |
| Count of Participants [Participants] |
107
70.9%
|
18
37.5%
|
| Title | Number of Participants Experiencing Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities Prior to Completion of the Oral Phase |
|---|---|
| Description | An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm. |
| Time Frame | Measured through Week 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 151 | 48 |
| Count of Participants [Participants] |
84
55.6%
|
25
52.1%
|
| Title | Number of Participants Willing to Use an Injectable Agent Such as the Study Product for HIV Prevention in the Future |
|---|---|
| Description | Stratified by Visit and Cohort |
| Time Frame | Measured from week 6 through Week 30 in cohort 1 and Week 34 in cohort 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Sample size varies by visit due to reasons such as missing visits and different schedules. |
| Arm/Group Title | Cohort 1 | Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants who were planned to receive IM injections of 744LA or placebo at three time points at 12 week intervals.Two sequential 400 mg gluteal injections were given at each injection visit (if not discontinued). | participants who were planned to receive IM injections of 744LA or placebo at five time points at 4 and 8 week intervals.One 600 mg gluteal injection was given at each injection visit (if not discontinued). |
| Measure Participants | 98 | 78 |
| Week 6 |
80
53%
|
74
154.2%
|
| Week 10 |
74
49%
|
|
| Week 18 |
81
53.6%
|
73
152.1%
|
| Week 26 |
71
47%
|
|
| Week 30 |
69
45.7%
|
|
| Week 34 |
65
43%
|
| Title | Number of Participants With HIV Infections Through the Study Period, Stratified by Arm |
|---|---|
| Description | |
| Time Frame | Measured through Week 105 for Cohort 1 and Week 109 for Cohort 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 151 | 48 |
| Count of Participants [Participants] |
1
0.7%
|
0
0%
|
| Title | Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period |
|---|---|
| Description | Week 29/31 is a combination of week 29, cohort 1 and week 33, cohort 2. The outcome in this table is stratified by arm. |
| Time Frame | Measured through Week 77 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis sample size is different at each visit due to multiple reasons (early termination, missing data, study unblinding, etc.) |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 151 | 48 |
| Enrollment Visit |
0.81
(0.46)
|
0.92
(0.65)
|
| Week 5 |
0.84
(0.44)
|
0.78
(0.67)
|
| Week 17 |
0.81
(0.54)
|
0.84
(0.57)
|
| Week 29/33 |
0.85
(0.57)
|
0.80
(0.46)
|
| Week 41 |
0.85
(0.66)
|
0.88
(0.45)
|
| Week 53 |
0.84
(0.62)
|
0.83
(0.50)
|
| Week 65 |
0.87
(0.76)
|
0.88
(0.48)
|
| Week 77 |
0.84
(0.61)
|
0.82
(0.50)
|
| Title | Number of Injectable Hormonal-contraception-using Female Participants Experiencing Grade 2 or Higher Clinical AE and Laboratory Abnormalities During Oral Phase |
|---|---|
| Description | An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm. |
| Time Frame | Measured through Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes injectable hormonal-contraception-using female participants in the study |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 34 | 13 |
| Count of Participants [Participants] |
17
11.3%
|
7
14.6%
|
| Title | Number of Injectable Hormonal-contraception-using Female Participants Experiencing Grade 2 or Higher Clinical AE and Laboratory Abnormalities During Injection Phase |
|---|---|
| Description | |
| Time Frame | Measured from first injection through 12 weeks after last injection for Cohort 1 and 8 weeks after last injection for Cohort 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes injectable hormonal-contraception-using female participants who received at least one injection of study drug in the study |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 32 | 12 |
| Count of Participants [Participants] |
29
19.2%
|
12
25%
|
| Title | Number of Injectable Hormonal-contraception-using Female Participants Who Discontinue Study Product for Reasons of Toxicity, Tolerability, or Acceptability During Oral Phase |
|---|---|
| Description | Stratified by arm |
| Time Frame | Measured through Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes injectable hormonal-contraception-using female participants in the study |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 34 | 13 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Number of Injectable Hormonal-contraception-using Female Participants Who Discontinue Study Product for Reasons of Toxicity, Tolerability, or Acceptability During Injection Phase |
|---|---|
| Description | |
| Time Frame | Measured from first injection through 12 weeks after last injection for Cohort 1 and 8 weeks after last injection for Cohort 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This population includes injectable hormonal-contraception-using female participants who received at least one injection of study drug in the study |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 32 | 12 |
| Count of Participants [Participants] |
3
2%
|
0
0%
|
| Title | Number of Participants Who Discontinue Oral Study Product for Reasons of Toxicity, Tolerability, or Acceptability Prior to Completion of the Oral Phase |
|---|---|
| Description | Stratified by arm |
| Time Frame | Measured through Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo |
|---|---|---|
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection |
| Measure Participants | 151 | 48 |
| Count of Participants [Participants] |
6
4%
|
0
0%
|
Adverse Events
| Time Frame | 41 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Group 1: GSK1265744 | Group 2: Placebo | ||
| Arm/Group Description | Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. GSK1265744 Tablets: 30-mg tablets, taken orally Injectable GSK1265744: Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections Cohort 2: 600-mg injection, administered as one IM gluteal injection | Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo-at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2. Placebo for GSK1265744 Tablets: Taken orally Injectable Placebo for GSK1265744: Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection | ||
All Cause Mortality |
||||
| Group 1: GSK1265744 | Group 2: Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/151 (0%) | 0/48 (0%) | ||
Serious Adverse Events |
||||
| Group 1: GSK1265744 | Group 2: Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/151 (2.6%) | 2/48 (4.2%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo positional | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholelithiasis | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Infections and infestations | ||||
| Laryngitis bacterial | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Nervous system disorders | ||||
| Sensory loss | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion spontaneous | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Group 1: GSK1265744 | Group 2: Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 147/151 (97.4%) | 48/48 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Hypochromic anaemia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Lymphopenia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Cardiac disorders | ||||
| Bradycardia | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Sinus arrhythmia | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Sinus bradycardia | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Tachycardia | 0/151 (0%) | 0 | 1/48 (2.1%) | 2 |
| Ear and labyrinth disorders | ||||
| Ear pain | 2/151 (1.3%) | 2 | 3/48 (6.3%) | 4 |
| External ear inflammation | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Motion sickness | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Vertigo | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Eye disorders | ||||
| Conjunctivitis allergic | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Eye irritation | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Eye pruritus | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Night blindness | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Photophobia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pseudopapilloedema | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Vision blurred | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Visual impairment | 0/151 (0%) | 0 | 2/48 (4.2%) | 2 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 2/151 (1.3%) | 3 | 0/48 (0%) | 0 |
| Abdominal distension | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Abdominal pain | 7/151 (4.6%) | 9 | 0/48 (0%) | 0 |
| Abdominal pain lower | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Abdominal pain upper | 3/151 (2%) | 4 | 1/48 (2.1%) | 1 |
| Anal fissure | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Chronic gastritis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Constipation | 5/151 (3.3%) | 6 | 2/48 (4.2%) | 2 |
| Defaecation urgency | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Diarrhoea | 13/151 (8.6%) | 16 | 6/48 (12.5%) | 10 |
| Dry mouth | 4/151 (2.6%) | 4 | 0/48 (0%) | 0 |
| Dyspepsia | 1/151 (0.7%) | 1 | 2/48 (4.2%) | 2 |
| Faeces soft | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Flatulence | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Food poisoning | 4/151 (2.6%) | 4 | 0/48 (0%) | 0 |
| Gastritis | 5/151 (3.3%) | 5 | 0/48 (0%) | 0 |
| Gastrooesophageal reflux disease | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Haematochezia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Haemorrhoids | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Mouth ulceration | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Nausea | 18/151 (11.9%) | 23 | 5/48 (10.4%) | 7 |
| Paraesthesia oral | 0/151 (0%) | 0 | 2/48 (4.2%) | 2 |
| Tongue coated | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Tooth impacted | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Toothache | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Trichoglossia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Umbilical hernia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Vomiting | 9/151 (6%) | 14 | 2/48 (4.2%) | 3 |
| General disorders | ||||
| Chest pain | 5/151 (3.3%) | 5 | 0/48 (0%) | 0 |
| Chills | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Complication associated with device | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Complication of device insertion | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Complication of device removal | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Fatigue | 11/151 (7.3%) | 15 | 6/48 (12.5%) | 7 |
| Feeling hot | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Feeling jittery | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Hunger | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Implant site pain | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Induration | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Inflammation | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Influenza like illness | 15/151 (9.9%) | 19 | 1/48 (2.1%) | 1 |
| Injection site bruising | 19/151 (12.6%) | 23 | 2/48 (4.2%) | 2 |
| Injection site dermatitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Injection site discomfort | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Injection site erythema | 10/151 (6.6%) | 16 | 0/48 (0%) | 0 |
| Injection site induration | 24/151 (15.9%) | 39 | 1/48 (2.1%) | 2 |
| Injection site nodule | 7/151 (4.6%) | 9 | 0/48 (0%) | 0 |
| Injection site pain | 120/151 (79.5%) | 567 | 11/48 (22.9%) | 29 |
| Injection site pruritus | 4/151 (2.6%) | 6 | 0/48 (0%) | 0 |
| Injection site reaction | 4/151 (2.6%) | 5 | 0/48 (0%) | 0 |
| Injection site swelling | 11/151 (7.3%) | 17 | 0/48 (0%) | 0 |
| Injection site warmth | 3/151 (2%) | 4 | 0/48 (0%) | 0 |
| Malaise | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Oedema peripheral | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Pain | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Puncture site pain | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pyrexia | 9/151 (6%) | 10 | 0/48 (0%) | 0 |
| Thirst | 1/151 (0.7%) | 2 | 1/48 (2.1%) | 1 |
| Vessel puncture site haematoma | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Vessel puncture site pain | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Xerosis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Immune system disorders | ||||
| Hypersensitivity | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Seasonal allergy | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Infections and infestations | ||||
| Acute sinusitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Bacterial vaginosis | 3/151 (2%) | 3 | 2/48 (4.2%) | 2 |
| Body tinea | 6/151 (4%) | 6 | 1/48 (2.1%) | 1 |
| Breast cellulitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Bronchitis | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Campylobacter infection | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Cellulitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Cervicitis | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Chikungunya virus infection | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Chlamydial infection | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Conjunctivitis | 7/151 (4.6%) | 8 | 1/48 (2.1%) | 1 |
| Conjunctivitis bacterial | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Conjunctivitis viral | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Cutaneous sporotrichosis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Escherichia urinary tract infection | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Fungal infection | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Fungal skin infection | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Furuncle | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Gastroenteritis | 4/151 (2.6%) | 5 | 2/48 (4.2%) | 2 |
| Gastroenteritis viral | 6/151 (4%) | 6 | 1/48 (2.1%) | 1 |
| Gastrointestinal infection | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Genital candidiasis | 2/151 (1.3%) | 3 | 0/48 (0%) | 0 |
| Genital herpes | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Genital infection fungal | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Genitourinary tract gonococcal infection | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Gingivitis | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Groin abscess | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Herpes zoster | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Hordeolum | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Infected bite | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Infection parasitic | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Influenza | 10/151 (6.6%) | 11 | 4/48 (8.3%) | 5 |
| Laryngitis bacterial | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Lower respiratory tract infection | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Malaria | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Mastoiditis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Molluscum contagiosum | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Nasopharyngitis | 8/151 (5.3%) | 8 | 4/48 (8.3%) | 7 |
| Oral herpes | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Oropharyngeal gonococcal infection | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Otitis externa | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Otitis media bacterial | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Paronychia | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Pelvic inflammatory disease | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Periorbital cellulitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pharyngitis | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Pharyngitis bacterial | 3/151 (2%) | 4 | 0/48 (0%) | 0 |
| Pneumonia bacterial | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Post procedural infection | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Postoperative wound infection | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Proctitis chlamydial | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pyelonephritis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Rhinitis | 3/151 (2%) | 3 | 2/48 (4.2%) | 2 |
| Schistosomiasis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Sinusitis | 5/151 (3.3%) | 6 | 1/48 (2.1%) | 1 |
| Sinusitis bacterial | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Subcutaneous abscess | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Tinea cruris | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Tinea infection | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Tinea versicolour | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Tonsillitis | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Tonsillitis bacterial | 4/151 (2.6%) | 4 | 1/48 (2.1%) | 1 |
| Tooth abscess | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Upper respiratory tract infection | 25/151 (16.6%) | 41 | 11/48 (22.9%) | 13 |
| Upper respiratory tract infection bacterial | 10/151 (6.6%) | 13 | 1/48 (2.1%) | 1 |
| Urethritis gonococcal | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Urinary tract infection | 9/151 (6%) | 11 | 2/48 (4.2%) | 2 |
| Urinary tract infection bacterial | 7/151 (4.6%) | 9 | 1/48 (2.1%) | 1 |
| Viral infection | 5/151 (3.3%) | 5 | 2/48 (4.2%) | 3 |
| Viral pharyngitis | 5/151 (3.3%) | 5 | 0/48 (0%) | 0 |
| Viral rhinitis | 6/151 (4%) | 9 | 0/48 (0%) | 0 |
| Viral tonsillitis | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Viral upper respiratory tract infection | 16/151 (10.6%) | 18 | 8/48 (16.7%) | 10 |
| Vulvovaginal candidiasis | 6/151 (4%) | 6 | 1/48 (2.1%) | 2 |
| Vulvovaginal mycotic infection | 3/151 (2%) | 4 | 0/48 (0%) | 0 |
| Vulvovaginitis | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Zika virus infection | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Arthropod bite | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Cartilage injury | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Chemical burn of skin | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Contusion | 6/151 (4%) | 7 | 1/48 (2.1%) | 1 |
| Exposure to toxic agent | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Eye injury | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Heat illness | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Human bite | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Hypobarism | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Injection related reaction | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Injury | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Joint dislocation | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Joint injury | 2/151 (1.3%) | 2 | 2/48 (4.2%) | 2 |
| Laceration | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Ligament sprain | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Limb injury | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Muscle strain | 2/151 (1.3%) | 2 | 2/48 (4.2%) | 2 |
| Post lumbar puncture syndrome | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Post procedural contusion | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Post procedural haematoma | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Post procedural swelling | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Procedural headache | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Procedural pain | 4/151 (2.6%) | 4 | 0/48 (0%) | 0 |
| Radius fracture | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Skin abrasion | 2/151 (1.3%) | 4 | 0/48 (0%) | 0 |
| Soft tissue injury | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Tendon injury | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Tooth fracture | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Toxicity to various agents | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 18/151 (11.9%) | 26 | 5/48 (10.4%) | 8 |
| Amylase decreased | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Amylase increased | 18/151 (11.9%) | 32 | 5/48 (10.4%) | 10 |
| Aspartate aminotransferase increased | 13/151 (8.6%) | 18 | 3/48 (6.3%) | 4 |
| Bilirubin conjugated increased | 7/151 (4.6%) | 10 | 1/48 (2.1%) | 1 |
| Blood alkaline phosphatase increased | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Blood bicarbonate decreased | 24/151 (15.9%) | 43 | 10/48 (20.8%) | 18 |
| Blood bilirubin increased | 3/151 (2%) | 5 | 3/48 (6.3%) | 5 |
| Blood calcium decreased | 9/151 (6%) | 10 | 4/48 (8.3%) | 8 |
| Blood calcium increased | 5/151 (3.3%) | 5 | 3/48 (6.3%) | 3 |
| Blood cholesterol increased | 5/151 (3.3%) | 5 | 0/48 (0%) | 0 |
| Blood creatine phosphokinase increased | 25/151 (16.6%) | 37 | 8/48 (16.7%) | 14 |
| Blood creatinine increased | 19/151 (12.6%) | 33 | 4/48 (8.3%) | 6 |
| Blood glucose decreased | 29/151 (19.2%) | 56 | 11/48 (22.9%) | 19 |
| Blood glucose increased | 56/151 (37.1%) | 99 | 21/48 (43.8%) | 39 |
| Blood magnesium decreased | 18/151 (11.9%) | 31 | 8/48 (16.7%) | 11 |
| Blood magnesium increased | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Blood phosphorus decreased | 25/151 (16.6%) | 38 | 10/48 (20.8%) | 17 |
| Blood potassium decreased | 8/151 (5.3%) | 11 | 1/48 (2.1%) | 1 |
| Blood potassium increased | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Blood pressure diastolic increased | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Blood pressure increased | 7/151 (4.6%) | 9 | 1/48 (2.1%) | 1 |
| Blood pressure systolic increased | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Blood sodium decreased | 8/151 (5.3%) | 9 | 1/48 (2.1%) | 1 |
| Blood sodium increased | 8/151 (5.3%) | 11 | 3/48 (6.3%) | 3 |
| Blood triglycerides increased | 7/151 (4.6%) | 7 | 1/48 (2.1%) | 1 |
| Carbon dioxide decreased | 8/151 (5.3%) | 15 | 3/48 (6.3%) | 5 |
| Creatinine renal clearance decreased | 71/151 (47%) | 168 | 21/48 (43.8%) | 47 |
| Electrocardiogram PR prolongation | 3/151 (2%) | 4 | 1/48 (2.1%) | 1 |
| Electrocardiogram QT prolonged | 7/151 (4.6%) | 13 | 3/48 (6.3%) | 4 |
| Electrocardiogram T wave inversion | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 2 |
| Electrocardiogram repolarisation abnormality | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Haemoglobin decreased | 6/151 (4%) | 11 | 1/48 (2.1%) | 3 |
| Heart rate increased | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Lipase increased | 23/151 (15.2%) | 34 | 14/48 (29.2%) | 26 |
| Low density lipoprotein increased | 9/151 (6%) | 9 | 2/48 (4.2%) | 2 |
| Lymphocyte count decreased | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Neutrophil count decreased | 2/151 (1.3%) | 3 | 1/48 (2.1%) | 2 |
| Platelet count decreased | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Protein urine | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Weight decreased | 2/151 (1.3%) | 4 | 3/48 (6.3%) | 4 |
| White blood cell count decreased | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Abnormal loss of weight | 4/151 (2.6%) | 5 | 0/48 (0%) | 0 |
| Decreased appetite | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Diabetes mellitus | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Hypercholesterolaemia | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Hyperglycaemia | 4/151 (2.6%) | 4 | 3/48 (6.3%) | 3 |
| Hypernatraemia | 2/151 (1.3%) | 2 | 2/48 (4.2%) | 2 |
| Hyperphagia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Hypocalcaemia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Hypoglycaemia | 7/151 (4.6%) | 12 | 1/48 (2.1%) | 2 |
| Hypokalaemia | 2/151 (1.3%) | 3 | 1/48 (2.1%) | 3 |
| Hypomagnesaemia | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Hyponatraemia | 0/151 (0%) | 0 | 2/48 (4.2%) | 2 |
| Hypophosphataemia | 6/151 (4%) | 8 | 1/48 (2.1%) | 2 |
| Increased appetite | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Iron deficiency | 3/151 (2%) | 4 | 0/48 (0%) | 0 |
| Metabolic syndrome | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Polydipsia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Vitamin D deficiency | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 11/151 (7.3%) | 13 | 3/48 (6.3%) | 3 |
| Arthritis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Arthrofibrosis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Back pain | 16/151 (10.6%) | 18 | 3/48 (6.3%) | 3 |
| Costochondritis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Exostosis | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Femoroacetabular impingement | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Intervertebral disc degeneration | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Joint stiffness | 1/151 (0.7%) | 3 | 0/48 (0%) | 0 |
| Ligament laxity | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Muscle spasms | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Muscle tightness | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Muscle twitching | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 2 |
| Muscular weakness | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Musculoskeletal chest pain | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Musculoskeletal discomfort | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Musculoskeletal pain | 13/151 (8.6%) | 14 | 4/48 (8.3%) | 5 |
| Musculoskeletal stiffness | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Myalgia | 16/151 (10.6%) | 19 | 4/48 (8.3%) | 7 |
| Neck pain | 8/151 (5.3%) | 8 | 0/48 (0%) | 0 |
| Pain in extremity | 10/151 (6.6%) | 10 | 2/48 (4.2%) | 2 |
| Patellofemoral pain syndrome | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Plantar fasciitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Rotator cuff syndrome | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Spondylitis | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Synovial cyst | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Synovitis | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Tendon pain | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Tendonitis | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Tenosynovitis stenosans | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Torticollis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Dysplastic naevus | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Nervous system disorders | ||||
| Disturbance in attention | 2/151 (1.3%) | 2 | 2/48 (4.2%) | 2 |
| Dizziness | 22/151 (14.6%) | 28 | 5/48 (10.4%) | 6 |
| Dysgeusia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Facial paralysis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Headache | 53/151 (35.1%) | 78 | 11/48 (22.9%) | 13 |
| Hypersomnia | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Hypoaesthesia | 7/151 (4.6%) | 10 | 1/48 (2.1%) | 1 |
| Intracranial pressure increased | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Lumbar radiculopathy | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Migraine | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Nerve compression | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Paraesthesia | 7/151 (4.6%) | 9 | 1/48 (2.1%) | 1 |
| Presyncope | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Seizure | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Somnolence | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Spinal cord compression | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Tension headache | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Tremor | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Vomiting in pregnancy | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Product Issues | ||||
| Device breakage | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Psychiatric disorders | ||||
| Abnormal dreams | 8/151 (5.3%) | 12 | 4/48 (8.3%) | 4 |
| Anxiety | 4/151 (2.6%) | 4 | 1/48 (2.1%) | 1 |
| Anxiety disorder | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Depressed mood | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Depression | 0/151 (0%) | 0 | 3/48 (6.3%) | 3 |
| Initial insomnia | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Insomnia | 13/151 (8.6%) | 18 | 2/48 (4.2%) | 2 |
| Irritability | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Libido decreased | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Mood altered | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Mood swings | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Sleep disorder | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Stress | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Renal and urinary disorders | ||||
| Dysuria | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Polyuria | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Proteinuria | 5/151 (3.3%) | 5 | 0/48 (0%) | 0 |
| Urinary hesitation | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Urinary incontinence | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Reproductive system and breast disorders | ||||
| Balanoposthitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Breast mass | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Cervical dysplasia | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Dysfunctional uterine bleeding | 4/151 (2.6%) | 4 | 2/48 (4.2%) | 2 |
| Dysmenorrhoea | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Dyspareunia | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Menorrhagia | 2/151 (1.3%) | 3 | 0/48 (0%) | 0 |
| Metrorrhagia | 1/151 (0.7%) | 2 | 0/48 (0%) | 0 |
| Oligomenorrhoea | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Ovarian cyst | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Testicular swelling | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Uterine haemorrhage | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Vaginal discharge | 5/151 (3.3%) | 5 | 0/48 (0%) | 0 |
| Vulvovaginal pruritus | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Allergic pharyngitis | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Allergic sinusitis | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Cough | 6/151 (4%) | 6 | 0/48 (0%) | 0 |
| Epistaxis | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Nasal congestion | 8/151 (5.3%) | 8 | 4/48 (8.3%) | 4 |
| Nasal inflammation | 0/151 (0%) | 0 | 1/48 (2.1%) | 2 |
| Nasal polyps | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Oropharyngeal pain | 5/151 (3.3%) | 5 | 1/48 (2.1%) | 1 |
| Pharyngeal erythema | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pharyngeal exudate | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Rhinitis allergic | 4/151 (2.6%) | 5 | 1/48 (2.1%) | 1 |
| Rhinorrhoea | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Sinus congestion | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Sinus pain | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Sneezing | 1/151 (0.7%) | 1 | 1/48 (2.1%) | 1 |
| Throat irritation | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Upper-airway cough syndrome | 0/151 (0%) | 0 | 1/48 (2.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Acne | 3/151 (2%) | 3 | 1/48 (2.1%) | 1 |
| Angioedema | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Blister | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Dermatitis | 3/151 (2%) | 3 | 2/48 (4.2%) | 2 |
| Dermatitis allergic | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Dermatitis atopic | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Dermatitis contact | 4/151 (2.6%) | 5 | 0/48 (0%) | 0 |
| Dry skin | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Eczema | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Erythema | 2/151 (1.3%) | 2 | 2/48 (4.2%) | 3 |
| Hyperhidrosis | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Intertrigo | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Papule | 2/151 (1.3%) | 2 | 1/48 (2.1%) | 1 |
| Penile ulceration | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Photosensitivity reaction | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Pruritus | 4/151 (2.6%) | 4 | 1/48 (2.1%) | 1 |
| Pruritus generalised | 3/151 (2%) | 4 | 0/48 (0%) | 0 |
| Rash | 4/151 (2.6%) | 4 | 1/48 (2.1%) | 1 |
| Rash erythematous | 0/151 (0%) | 0 | 1/48 (2.1%) | 2 |
| Rash macular | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Rash maculo-papular | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Rash papular | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Rash pruritic | 3/151 (2%) | 3 | 0/48 (0%) | 0 |
| Seborrhoea | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Skin erosion | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Skin odour abnormal | 1/151 (0.7%) | 1 | 0/48 (0%) | 0 |
| Urticaria | 4/151 (2.6%) | 8 | 2/48 (4.2%) | 2 |
| Urticaria papular | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
| Vascular disorders | ||||
| Essential hypertension | 1/151 (0.7%) | 3 | 0/48 (0%) | 0 |
| Hypertension | 8/151 (5.3%) | 8 | 0/48 (0%) | 0 |
| Orthostatic hypotension | 2/151 (1.3%) | 2 | 0/48 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
| Name/Title | Gordon Chau |
|---|---|
| Organization | Fred Hutch Cancer Research Center |
| Phone | 2066672118 |
| gchau@fredhutch.org |
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02178800
Other Study ID Numbers:
- HPTN 077
- 11964
First Posted:
Jul 1, 2014
Last Update Posted:
Oct 18, 2021
Last Verified:
Oct 1, 2021