Trial Outcomes & Findings for A Trial to Evaluate the Correlation Between Spontaneous Catch-up Growth, Clinical Response to Saizen (Recombinant Human Growth Hormone, r-hGH) and Gene Expression Profiling in Children Small for Gestational Age (SGA) (NCT NCT01067352)

Last Updated: 2013-12-27

Results Overview

Gene expression profiling:analysis of ribonucleic acid (RNA) extracted from body tissue or fluids using Clontech Atlas Human Array to study level of activation of genes in tissue analyzed. Analysis was performed to identify possible correlation between catch-up growth (either spontaneous or drug-induced after Week 48) and therapeutic response to rhGH. Spontaneous catch up growth:shown by SGA participants having length more than third percentile at Week 96 without any treatment;drug induced growth was by SGA participants having length more than third percentile at Week 96 with drug treatment.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

25 participants

Primary outcome timeframe

Baseline and Week 48

Results posted on

2013-12-27

Participant Flow

Participants were recruited in 12 study centers in Italy from 20 Feb 2004 to 10 Jul 2009.

Participant milestones

Participant milestones
Measure	Group A, Less Than Third Percentile (Saizen) Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received Saizen (recombinant human growth hormone, r-hGH) subcutaneously (s.c) at the daily dose of 0.035 milligram(mg)/kilogram(kg) for 2 years.	Group A2, Less Than Third Percentile (No Treatment) Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.	Group B, More Than Third Percentile (No Treatment) Participants with more than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.
Overall Study STARTED	9	6	10
Overall Study COMPLETED	8	3	9
Overall Study NOT COMPLETED	1	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A, Less Than Third Percentile (Saizen) Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received Saizen (recombinant human growth hormone, r-hGH) subcutaneously (s.c) at the daily dose of 0.035 milligram(mg)/kilogram(kg) for 2 years.	Group A2, Less Than Third Percentile (No Treatment) Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.	Group B, More Than Third Percentile (No Treatment) Participants with more than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.
Overall Study Withdrawal by Subject	1	2	1
Overall Study Physician Decision	0	1	0

Baseline Characteristics

A Trial to Evaluate the Correlation Between Spontaneous Catch-up Growth, Clinical Response to Saizen (Recombinant Human Growth Hormone, r-hGH) and Gene Expression Profiling in Children Small for Gestational Age (SGA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A, Less Than Third Percentile (Saizen) n=9 Participants Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received Saizen (recombinant human growth hormone, r-hGH) subcutaneously (s.c) at the daily dose of 0.035 milligram(mg)/kilogram(kg) for 2 years.	Group A2, Less Than Third Percentile (No Treatment) n=6 Participants Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.	Group B, More Than Third Percentile (No Treatment) n=10 Participants Participants with more than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.	Total n=25 Participants Total of all reporting groups
Age, Continuous	5.7 years STANDARD_DEVIATION 1.2 • n=5 Participants	5.0 years STANDARD_DEVIATION 0.7 • n=7 Participants	5.2 years STANDARD_DEVIATION 0.4 • n=5 Participants	5.3 years STANDARD_DEVIATION 0.9 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 48

Population: Gene expression profiling was not performed due to RNA degradation in nearly all of the blood samples and hence no comparison between gene expression and growth was made.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through Week 96

Population: Data was not analyzed due to small number of evaluable participants.

Spontaneous catch up growth was the growth shown by SGA participants having length more than third percentile at Week 96 without any study drug treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through Week 96

Population: Safety analysis population included all randomized participants with at least 1 post-baseline assessment.

AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug , SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued from the study due to AE were also recorded.

Outcome measures

Outcome measures
Measure	Group A, Less Than Third Percentile (Saizen) n=8 Participants Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received Saizen (recombinant human growth hormone, r-hGH) subcutaneously (s.c) at the daily dose of 0.035 milligram(mg)/kilogram(kg) for 2 years.	Group A2, Less Than Third Percentile (No Treatment) n=4 Participants Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.	Group B, More Than Third Percentile (No Treatment) n=10 Participants Participants with more than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation AEs	6 participants	4 participants	9 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation SAEs	0 participants	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation Discontinuation due to AEs	0 participants	0 participants	0 participants

Adverse Events

Group A, Less Than Third Percentile (Saizen)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Group A2, Less Than Third Percentile (No Treatment)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Group B, More Than Third Percentile (No Treatment)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Responsible

Merck Serono S.p.A., Italy, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Group A, Less Than Third Percentile (Saizen) n=8 participants at risk Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received Saizen (recombinant human growth hormone, r-hGH) subcutaneously (s.c) at the daily dose of 0.035 milligram(mg)/kilogram(kg) for 2 years.	Group A2, Less Than Third Percentile (No Treatment) n=4 participants at risk Participants with less than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.	Group B, More Than Third Percentile (No Treatment) n=10 participants at risk Participants with more than third percentile for height (according to the Tanner reference table) at the age of 4-6 years received no drug treatment for 2 years.
General disorders Pyrexia	75.0% 6/8 • Number of events 15 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	50.0% 2/4 • Number of events 6 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	40.0% 4/10 • Number of events 6 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Ear infection	12.5% 1/8 • Number of events 3 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Bronchitis	25.0% 2/8 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	30.0% 3/10 • Number of events 4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Pharyngitis	12.5% 1/8 • Number of events 4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	50.0% 2/4 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	20.0% 2/10 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Blood and lymphatic system disorders Iron deficiency anaemia	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Blood and lymphatic system disorders Microcytic anaemia	12.5% 1/8 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Eye disorders Conjunctivitis	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Gastrointestinal disorders Stomatitis	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Gastrointestinal disorders Constipation	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
General disorders Cyst	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Rhinitis	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Gastroenteritis	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Tonsillitis	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Varicella	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	50.0% 2/4 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	20.0% 2/10 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Enterocolitis infectious	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Influenza	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	30.0% 3/10 • Number of events 3 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Infections and infestations Laryngitis	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Investigations Blood alkaline phosphatase increased	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Investigations Blood cholesterol increased	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Investigations Lipoprotein (a) abnormal	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Investigations Blood insulin decreased	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Immune system disorders Milk allergy	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	25.0% 1/4 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Musculoskeletal and connective tissue disorders Neck pain	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Nervous system disorders Headache	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Renal and urinary disorders Proteinuria	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Respiratory, thoracic and mediastinal disorders Cough	12.5% 1/8 • Number of events 4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	20.0% 2/10 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	25.0% 2/8 • Number of events 2 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Skin and subcutaneous tissue disorders Alopecia	12.5% 1/8 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/10 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Skin and subcutaneous tissue disorders Acute generalised exanthematous pustulosis	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/8 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	0.00% 0/4 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.	10.0% 1/10 • Number of events 1 • AEs were collected on an ongoing basis from day of written informed consent. All new AEs were recorded until the post-treatment safety, on Day 30 post-drug administration.