Trial Outcomes & Findings for ATX-GD-59 in Patients With Graves Disease Not Treated With Anti-thyroid Therapy (NCT NCT02973802)

NCT ID: NCT02973802

Last Updated: 2019-06-14

Results Overview

An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: 22 weeks
• Results posted on: 2019-06-14

Participant Flow

This study enrolled patients diagnosed with Graves Disease from 8 hospital clinics located in the UK. The last patient enrolled completed dosing in February 2018.

28 subjects were screened for the study, of which 12 were eligible, and commenced treatment with ATX-GD-59.

Participant milestones

Measure	ATX-GD-59 Treatment An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Overall Study STARTED	12
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	ATX-GD-59 Treatment An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

ATX-GD-59 in Patients With Graves Disease Not Treated With Anti-thyroid Therapy

Baseline characteristics by cohort

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	42.7 years STANDARD_DEVIATION 9.69 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 22 weeks

Population: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria. The Safety population was denoted as the 'Intention-to-treat population' for the summarisation of safety endpoints.

An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug

Outcome measures

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Total Adverse Events	311 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Mild Adverse Events	293 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Moderate Adverse Events	18 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Severe Adverse Events	0 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Drug Related Adverse Events	180 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Total Serious Adverse Events	3 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Drug Related Serious Events	1 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Adverse Events leading to death	0 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Adverse Events leading to early study withdrawal	0 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Events leading to dose interruption or suspension	0 Adverse Events
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. Treatment emergent injection related reaction	153 Adverse Events

SECONDARY outcome

Timeframe: Weeks 18, 22 and 30

Population: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.

Outcome measures

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII) Change from baseline at week 18	-0.7737 IU/L Standard Deviation 1.55475
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII) Change from baseline at week 22	-0.6602 IU/L Standard Deviation 1.35220
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII) Change from baseline at week 30	-0.8971 IU/L Standard Deviation 1.67639

SECONDARY outcome

Timeframe: Weeks 18, 22 and 30

Population: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al.

TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).

Outcome measures

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb) Change from baseline at week 18	-92.7 %SRR Standard Deviation 145.73
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb) Change from baseline at week 22	-54.0 %SRR Standard Deviation 118.94
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb) Change from baseline at week 30	-39.3 %SRR Standard Deviation 125.36

SECONDARY outcome

Timeframe: Weeks 18, 22 and 30

Population: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al.

TBAb activity is measured by calculating percentage inhibition.

Outcome measures

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb) Change from baseline at week 18	12.9 % Inhibition Standard Deviation 46.50
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb) Change from baseline at week 22	7.0 % Inhibition Standard Deviation 55.54
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb) Change from baseline at week 30	-0.1 % Inhibition Standard Deviation 60.49

SECONDARY outcome

Timeframe: Weeks 18, 22 and 30

Population: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.

Outcome measures

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22. Change from baseline at week 18	-11.75 Percent change Standard Deviation 26.513
Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22. Change from baseline at week 22	-14.19 Percent change Standard Deviation 25.549
Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22. Change from baseline at week 30	-15.79 Percent change Standard Deviation 27.367

SECONDARY outcome

Timeframe: Weeks 18, 22 and 30

Population: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.

Outcome measures

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Change in Serum Free Thyroxine (T4) From Baseline to Week 22. Change from baseline at week 18	-9.80 Percent change Standard Deviation 24.622
Change in Serum Free Thyroxine (T4) From Baseline to Week 22. Change from baseline at week 22	-14.54 Percent change Standard Deviation 20.011
Change in Serum Free Thyroxine (T4) From Baseline to Week 22. Change from baseline at week 30	-9.24 Percent change Standard Deviation 27.368

SECONDARY outcome

Timeframe: Weeks 18, 22 and 30

Population: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol

Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.

Outcome measures

Measure	ATX-GD-59 Treatment n=12 Participants An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22. Change from baseline at week 18	0.267 mIU/L Standard Deviation 0.8028
Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22. Change from baseline at week 22	0.309 mIU/L Standard Deviation 0.8398
Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22. Change from baseline at week 30	0.473 mIU/L Standard Deviation 1.1915

SECONDARY outcome

Timeframe: weeks 0, 18 and 22

Population: No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: weeks 0, 18 and 22

Population: No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: weeks 0, 18 and 22

Population: No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.

Outcome measures

Outcome data not reported

Adverse Events

Treatment Emergent Adverse Events

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Non Treatment Emergent Adverse Events

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment Emergent Adverse Events n=12 participants at risk Treatment emergent adverse events were any adverse events that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of ATX-GD-59	Non Treatment Emergent Adverse Events n=12 participants at risk Any non-treatment emergent adverse events.
Gastrointestinal disorders Mild Nausea	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Vomiting	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Cardiac disorders Paroxysmal Atrial Fibrillationion	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Non-Cardiac Chest Pain	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.

Other adverse events

Measure	Treatment Emergent Adverse Events n=12 participants at risk Treatment emergent adverse events were any adverse events that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of ATX-GD-59	Non Treatment Emergent Adverse Events n=12 participants at risk Any non-treatment emergent adverse events.
General disorders Injection site erythema	83.3% 10/12 • Number of events 61 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Injection site swelling	66.7% 8/12 • Number of events 46 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Injection site pain	50.0% 6/12 • Number of events 27 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Injection site pruritus	25.0% 3/12 • Number of events 7 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Injection site rash	16.7% 2/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Injection site urticaria	16.7% 2/12 • Number of events 9 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Pyrexia	16.7% 2/12 • Number of events 12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Asthenia	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Fatigue	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Feeling hot	8.3% 1/12 • Number of events 3 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Injection site discomfort	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Malaise	8.3% 1/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Non-cardiac chest pain	8.3% 1/12 • Number of events 9 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Oedema	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Peripheral swelling	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Suprapubic Pain	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
General disorders Thirst	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Urinary tract infection	16.7% 2/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Nasopharyngitis	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Onychomycosis	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Oral herpes	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Rhinitis	8.3% 1/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Upper respiratory tract infection	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Urinary tract infection bacterial	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Infections and infestations Vulvovaginal candidiasis	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 2/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Musculoskeletal and connective tissue disorders Back pain	16.7% 2/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Musculoskeletal and connective tissue disorders Myalgia	16.7% 2/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Musculoskeletal and connective tissue disorders Bone pain	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Musculoskeletal and connective tissue disorders Muscle twitching	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.3% 1/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Musculoskeletal and connective tissue disorders Osteoporosis	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 4/12 • Number of events 7 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	25.0% 3/12 • Number of events 4 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 1/12 • Number of events 4 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Productive cough	8.3% 1/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Throat irritation	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Throat tightness	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Diarrhoea	25.0% 3/12 • Number of events 4 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Vomiting	25.0% 3/12 • Number of events 10 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Nausea	16.7% 2/12 • Number of events 13 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Abdominal pain lower	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Abdominal tenderness	8.3% 1/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Haematochezia	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Gastrointestinal disorders Toothache	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Nervous system disorders Dizziness	33.3% 4/12 • Number of events 19 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Nervous system disorders Headache	25.0% 3/12 • Number of events 10 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Nervous system disorders Dysgeusia	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Nervous system disorders Migraine	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Nervous system disorders Paraesthesia	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Cardiac disorders Palpitations	16.7% 2/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Cardiac disorders Angina pectoris	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Cardiac disorders Atrial fibulation	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Cardiac disorders Atrioventricular block first degree	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Cardiac disorders Tachycardia	8.3% 1/12 • Number of events 4 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Injury, poisoning and procedural complications Injection related reaction	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Injury, poisoning and procedural complications Procedural pain	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Injury, poisoning and procedural complications Wrist fracture	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Skin and subcutaneous tissue disorders Dermal cyst	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Skin and subcutaneous tissue disorders Erythema	8.3% 1/12 • Number of events 2 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Skin and subcutaneous tissue disorders Rash	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Investigations Blood uric acid increased	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Investigations Eosinophil count increased	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Investigations Lymph node palpable	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Investigations Respiratory rate increased	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Psychiatric disorders Anxiety	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Psychiatric disorders Depression	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Eye disorders Eyelid oedema	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Eye disorders Ocular hyperaemia	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Hepatobiliary disorders Hepatic steatosis	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Immune system disorders Seasonal allergy	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Metabolism and nutrition disorders Hypoglycaemia	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Renal and urinary disorders Dysuria	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Reproductive system and breast disorders Pelvic discomfort	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Vascular disorders Hot flush	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Nervous system disorders Possible Loss of Consciousness	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Respiratory, thoracic and mediastinal disorders Increased bronchial secretion	0.00% 0/12 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from screening through to the final follow up visit at week 30. Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.

Additional Information

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Results disclosure agreements

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