Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer (NCT NCT00494442)

Last Updated: 2018-08-01

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.

Results posted on

2018-08-01

Participant Flow

The first patient was enrolled on June 11, 2007 and efficacy and safety data were collected up to the data cut-off of March 17, 2009. Patients were enrolled at 12 centres in 5 countries: Australia, Germany, Spain, Sweden and the USA.

Two cohorts of women with Breast Cancer gene 1 (BRCA1)- or BRCA2-associated ovarian cancer who had failed at least one prior chemotherapy in the advanced/metastatic setting, were planned to receive olaparib 100 mg bd (n= up to 24) or 400 mg bd (n= up to 40). Enrolment to 2 cohorts was sequential with the 400 mg bd cohort being recruited first.

Participant milestones

Participant milestones
Measure	Olaparib 100 mg bd olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Overall Study STARTED	24	33
Overall Study COMPLETED	7	17
Overall Study NOT COMPLETED	17	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Olaparib 100 mg bd olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Overall Study Death	1	1
Overall Study Lack of Efficacy	16	10
Overall Study Adverse Event	0	2
Overall Study Physician Decision	0	1
Overall Study Non-compliance	0	1
Overall Study Intercurrent illness	0	1

Baseline Characteristics

Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olaparib 100 mg bd n=24 Participants olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 Participants olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily	Total n=57 Participants Total of all reporting groups
Age, Continuous	55.6 Years STANDARD_DEVIATION 8.02 • n=5 Participants	56.8 Years STANDARD_DEVIATION 10.49 • n=7 Participants	56 Years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	33 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
BRCA mutation BRCA1	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
BRCA mutation BRCA2	5 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.

Population: PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)

Outcome measures

Outcome measures
Measure	Olaparib 100 mg bd n=24 Participants olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 Participants olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) PP Analysis Set	3 Participants	11 Participants
Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) ITT Analysis Set	3 Participants	11 Participants

SECONDARY outcome

Timeframe: End of study

Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)

Outcome measures

Outcome measures
Measure	Olaparib 100 mg bd n=24 Participants olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 Participants olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Clinical Benefit (CB)	45.5 Percentage of participants Interval 26.9 to 65.3	71.0 Percentage of participants Interval 53.4 to 83.9

SECONDARY outcome

Timeframe: End of study

Duration of response to olaparib

Outcome measures

Outcome measures
Measure	Olaparib 100 mg bd n=24 Participants olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 Participants olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Duration of Response	242 Days Interval 169.0 to 288.0	301 Days Interval 126.0 to 506.0

SECONDARY outcome

Timeframe: End of study

The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).

Outcome measures

Outcome measures
Measure	Olaparib 100 mg bd n=24 Participants olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 Participants olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Best Percentage Change in Tumour Size	-5.1 Percent change Interval -85.7 to 66.1	-25.8 Percent change Interval -100.0 to 150.0

SECONDARY outcome

Timeframe: End of study

Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.

Outcome measures

Outcome measures
Measure	Olaparib 100 mg bd n=24 Participants olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 Participants olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Progression-Free Survival (PFS)	62.5 Days Interval 56.0 to 113.0	226 Days Interval 105.0 to 338.0

Adverse Events

Olaparib 100 mg bd

Serious events: 7 serious events

Other events: 23 other events

Deaths: 10 deaths

Olaparib 400 mg bd

Serious events: 12 serious events

Other events: 33 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Gerard Lynch

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review and comment prior to publication. In order to ensure that the Sponsor will be able to make comments and suggestions where pertinent, material for public dissemination will be submittted to the Sponsor for review at least sixty (60) days prior to submission for publication, public dissemination, or review by a publication committee
Publication restrictions are in place

Restriction type: OTHER

Measure	Olaparib 100 mg bd n=24 participants at risk olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 participants at risk olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Blood and lymphatic system disorders Neutropenia	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Blood and lymphatic system disorders Anaemia	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Cardiac disorders Cardiac Failure Congestive	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Nausea	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Vomiting	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Abdominal Pain	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Large Intestinal Obstruction	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Gastrointestinal Obstruction	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Ileus	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Intestinal Perforation	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
General disorders Oedema Peripheral	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Hepatobiliary disorders Bile Duct Stone	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Pneumonia	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Injury, poisoning and procedural complications Blood Pressure Increased	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Hyponatraemia	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Dehydration	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Nervous system disorders Encephalopathy	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Nervous system disorders Convulsion	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Psychiatric disorders Mental Status Changes	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Renal and urinary disorders Renal Failure	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Renal and urinary disorders Renal Failure Acute	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Vascular disorders Deep Vein Thrombosis	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.

Measure	Olaparib 100 mg bd n=24 participants at risk olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily	Olaparib 400 mg bd n=33 participants at risk olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Blood and lymphatic system disorders Neutropenia	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Nausea	62.5% 15/24 • From baseline, every visit until 30 days after last dose.	63.6% 21/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Blood and lymphatic system disorders Anaemia	12.5% 3/24 • From baseline, every visit until 30 days after last dose.	21.2% 7/33 • From baseline, every visit until 30 days after last dose.
Blood and lymphatic system disorders Lymphopenia	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Blood and lymphatic system disorders Thrombocytopenia	12.5% 3/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Diarrhoea	29.2% 7/24 • From baseline, every visit until 30 days after last dose.	36.4% 12/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Abdominal Pain	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	27.3% 9/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Vomiting	25.0% 6/24 • From baseline, every visit until 30 days after last dose.	33.3% 11/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Constipation	25.0% 6/24 • From baseline, every visit until 30 days after last dose.	12.1% 4/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Abdominal Distension	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	18.2% 6/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Dyspepsia	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	12.1% 4/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Abdominal Pain Upper	12.5% 3/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Abdominal Discomfort	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Gastrointestinal Pain	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Ascites	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Gastritis	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Rectal Haemorrhage	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Salivary Hypersecretion	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Gastrointestinal disorders Stomatitis	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
General disorders Fatigue	54.2% 13/24 • From baseline, every visit until 30 days after last dose.	51.5% 17/33 • From baseline, every visit until 30 days after last dose.
General disorders Oedema Peripheral	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	18.2% 6/33 • From baseline, every visit until 30 days after last dose.
General disorders Pyrexia	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
General disorders Asthenia	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Urinary Tract Infection	20.8% 5/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Upper Respiratory Tract Infection	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Oral Herpes	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Cellulitis	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Herpes Zoster	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Nasopharyngitis	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Infections and infestations Sinusitis	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Injury, poisoning and procedural complications Contusion	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	12.1% 4/33 • From baseline, every visit until 30 days after last dose.
Investigations Waist Circumference Increased	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Investigations Haemoglobin Urine	12.5% 3/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Investigations Blood Urine Present	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Investigations Gamma-Glutamyltransferase Increased	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Hypokalaemia	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	12.1% 4/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Hypomagnesaemia	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	12.1% 4/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Anorexia	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Hyperkalaemia	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Metabolism and nutrition disorders Decreased Appetite	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Musculoskeletal and connective tissue disorders Back Pain	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	12.1% 4/33 • From baseline, every visit until 30 days after last dose.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Musculoskeletal and connective tissue disorders Flank Pain	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Musculoskeletal and connective tissue disorders Joint Swelling	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Nervous system disorders Headache	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	21.2% 7/33 • From baseline, every visit until 30 days after last dose.
Nervous system disorders Neuropathy Peripheral	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Nervous system disorders Dizziness	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Nervous system disorders Dysgeusia	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Nervous system disorders Sinus Headache	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Psychiatric disorders Insomnia	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	12.1% 4/33 • From baseline, every visit until 30 days after last dose.
Psychiatric disorders Depression	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	9.1% 3/33 • From baseline, every visit until 30 days after last dose.
Psychiatric disorders Anxiety	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Renal and urinary disorders Pollakiuria	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Reproductive system and breast disorders Pelvic Pain	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 4/24 • From baseline, every visit until 30 days after last dose.	0.00% 0/33 • From baseline, every visit until 30 days after last dose.
Respiratory, thoracic and mediastinal disorders Cough	12.5% 3/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	0.00% 0/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	4.2% 1/24 • From baseline, every visit until 30 days after last dose.	6.1% 2/33 • From baseline, every visit until 30 days after last dose.
Skin and subcutaneous tissue disorders Rash	20.8% 5/24 • From baseline, every visit until 30 days after last dose.	15.2% 5/33 • From baseline, every visit until 30 days after last dose.
Skin and subcutaneous tissue disorders Dry Skin	8.3% 2/24 • From baseline, every visit until 30 days after last dose.	3.0% 1/33 • From baseline, every visit until 30 days after last dose.