Trial Outcomes & Findings for Study of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate (NCT NCT01783015)

Results Overview

DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the c-reactive protein (CRP) and Subject General Health Visual Analogue Scale (VAS) assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

16 participants

Primary outcome timeframe

Baseline, 12 weeks

Results posted on

2016-01-06

Participant Flow

In this 24 week, multicenter, randomized, double-blind, placebo-controlled (Period 1), 2 period study, a total of 20 participants were screened, out of which 16 participants were randomized. Due to delayed enrollment and an insufficient number of participants, recruitment was terminated.

Eleven participants were randomly assigned to etanercept \[ETN\] and 5 participants to placebo in the blinded treatment period. A total of 11 participants (9 ETN treated and 2 placebo treated) completed the blinded treatment period and entered the open label treatment with ETN. One of the 2 placebo treated participants entered the Escape Arm.

Participant milestones

Participant milestones
Measure	Period I - Blinded Treatment - Etanercept Participants received etanercept 50 mg subcutaneously with oral methotrexate tablets once-weekly.	Period I - Blinded Treatment - Placebo Participants received placebo injections with oral methotrexate tablets once-weekly.	Period 2 - Open Label Treatment Participants received etanercept 50 mg subcutaneously with oral methotrexate 10 to 25 mg once-weekly.
Blinded Treatment STARTED	11	5	0
Blinded Treatment Treated	11	5	0
Blinded Treatment COMPLETED	9	2	0
Blinded Treatment NOT COMPLETED	2	3	0
Open Label Treatment STARTED	0	0	11
Open Label Treatment COMPLETED	0	0	5
Open Label Treatment NOT COMPLETED	0	0	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Period I - Blinded Treatment - Etanercept Participants received etanercept 50 mg subcutaneously with oral methotrexate tablets once-weekly.	Period I - Blinded Treatment - Placebo Participants received placebo injections with oral methotrexate tablets once-weekly.	Period 2 - Open Label Treatment Participants received etanercept 50 mg subcutaneously with oral methotrexate 10 to 25 mg once-weekly.
Blinded Treatment Adverse Event	0	1	0
Blinded Treatment Protocol Violation	0	1	0
Blinded Treatment Withdrawal by Subject	0	1	0
Blinded Treatment Study Terminated by Sponsor	2	0	0
Open Label Treatment Study Terminated by Sponsor	0	0	6

Baseline Characteristics

Study of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Period I - Blinded Treatment - Etanercept n=11 Participants Participants received etanercept 50 mg subcutaneously with oral methotrexate tablets once-weekly.	Period I - Blinded Treatment - Placebo n=5 Participants Participants received placebo injections with oral methotrexate tablets once-weekly.	Total n=16 Participants Total of all reporting groups
Age, Continuous	54.5 Years STANDARD_DEVIATION 13.43 • n=5 Participants	54.8 Years STANDARD_DEVIATION 19.56 • n=7 Participants	54.6 Years STANDARD_DEVIATION 14.91 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the c-reactive protein (CRP) and Subject General Health Visual Analogue Scale (VAS) assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

DAS28 calculated from the number of SJC and PJC using the 28 joints count, the CRP and and Subject General Health VAS assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Number of participants with DAS28 \<3.2. A score of \< 3.2 implied low disease activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Number of Participants with DAS28 \<2.6. A DAS28 \< 2.6 implies remission.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant's assessment of pain; Subject Global Assessment (SGA) of disease activity; Physician Global Assessment (PGA) of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and CRP.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and ≥ 50% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and ≥ 70% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and ≥ 90% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

The Disease Activity Score Based on 28-joints Count based (DAS28-based) EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

The CDAI is the numerical sum of 4 outcome parameters: tender joint count (TJC) and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity. CDAI total score = 0-76. CDAI \<= 2.8 indicates disease remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

The SDAI is the numerical sum of five outcome parameters: TJC) and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity, and CRP (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Change from Baseline in CDAI scores was to be calculated. The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity. CDAI total score = 0-76. CDAI \<= 2.8 indicates disease remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Change from Baseline in SDAI scores were to be calculated. The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity, and CRP (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Change from Baseline in the number of tender/painful joints using the 28 joint count including shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees was to be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Change from Baseline in the number of swollen joints including shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees was to be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Change from Baseline in the PGA scores was to be estimated. The Study Physician estimated the participant's overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Change from Baseline in Subject Global Assessment of Disease Activity was to be estimated. Participants were to assess their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Subject General Health VAS assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Subject Pain was to be measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no pain and 100 mm = most severe pain.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

The EuroQol-5 Dimensions (EQ-5D) is a participant-completed questionnaire designed to assess health related quality of life. There are 2 components to the EQ-5D: a Health State Profile and a VAS. For the Health State Profile, participants recorded their level of current health for 5 domains comprising a health profile: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from the 5 domains may be used to calculate a single index value, also known as a utility score. On the VAS participants were asked to rate their current health on a scale from 0 to 100 mm, where 0 represented the "worst imaginable health state" and 100 represented the "best imaginable health state." In addition to a summary of mean changes, 1 categorical endpoint each based on EQ-5D utility score and 1 based on the VAS were derived and analyzed: EQ-5D utility score improvement ≥0.05 and EQ-5D VAS score \>82.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

The 36-Item Short Form Health Survey (SF-36) is widely used 36-item questionnaire that measures general health-related quality of life in the following 8 domains: physical function, role limitations due to physical health, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. Scores for the 8 domains range from 0 to 100 where higher scores are better.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

The Patient Acceptable Symptom State (PASS) was a participant-completed form in which participants were asked to "Think about all the ways your rheumatoid arthritis (RA) has affected you during the last 48 hours. If you were to remain in the next few months as you were during the last 48 hours, would this be acceptable or unacceptable to you?" The participant indicated a response of either "acceptable" or "unacceptable".

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Vectra disease activity analysis of laboratory samples was not conducted due to study termination.

The change from Baseline in Vectra disease activity levels was to be estimated. The assessment measures serum protein biomarkers associated with RA. It has a range from 1-100 with lower scores indicating the better outcome.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Blood samples (6 mL) were collected at the baseline, Week 12, and Week 24 visits, or upon early withdrawal, to provide a minimum of 1 mL serum each for ETN ADA and ETN neutralizing antibody analyses. Samples which were positive for ETN anti-drug antibodies were then also tested for ETN neutralizing antibodies.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks, 24 weeks

Population: Due to small sample size, Pfizer did not perform statistical analysis.

Blood samples (6 mL) were collected at the baseline, Week 12, and Week 24 visits, or upon early withdrawal, to provide a minimum of 1 mL serum each for ETN ADA and ETN neutralizing antibody analyses. Samples which were positive for ETN anti-drug antibodies were then also tested for ETN neutralizing antibodies.

Outcome measures

Outcome data not reported

Adverse Events

Period I - Blinded Treatment - Etanercept

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Period I - Blinded Treatment - Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Period 2 - Open Label Treatment

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Period I - Blinded Treatment - Etanercept n=11 participants at risk Participants received etanercept 50 mg subcutaneously with oral methotrexate tablets once-weekly.	Period I - Blinded Treatment - Placebo n=5 participants at risk Participants received placebo injections with oral methotrexate tablets once-weekly.	Period 2 - Open Label Treatment n=11 participants at risk Participants received etanercept 50 mg subcutaneously with oral methotrexate 10 to 25 mg once-weekly.
Blood and lymphatic system disorders ANAEMIA	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.0% 1/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Ear and labyrinth disorders TINNITUS	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.0% 1/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders DYSPEPSIA	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.0% 1/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders GASTROINTESTINAL DISORDER	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders NAUSEA	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.0% 1/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders INJECTION SITE ERYTHEMA	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders INJECTION SITE REACTION	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations NASOPHARYNGITIS	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations RHINITIS	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.0% 1/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations TONSILLITIS	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations TOOTH INFECTION	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations URINARY TRACT INFECTION	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders TENDONITIS	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders RHINORRHOEA	18.2% 2/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders DERMATITIS	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.0% 1/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Vascular disorders HYPERTENSION	0.00% 0/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/5 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.1% 1/11 • From the day the first dose of the investigational product was administered up to 28 days after last dose was administered. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.