An Open-Label, Phase 1b Study of Acalabrutinib With and Without Dexamethasone in Subjects With Multiple Myeloma

• Sponsor: Acerta Pharma BV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02211014
• Collaborator: Acerta Pharma, LLC (Other)
• Enrollment: 27
• Locations: 3
• Arms: 2
• Actual Duration (Months): 50.8
• Patients Per Site: 9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To characterize the safety profile of acalabrutinib with and without dexamethasone in subjects with relapsed or refractory Multiple Myeloma (MM)

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma (MM)	Drug: acalabrutinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Phase 1b Study of ACP-196 With and Without Dexamethasone in Subjects With Multiple Myeloma
• Actual Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Apr 26, 2019
• Actual Study Completion Date: Apr 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Acalabrutinib 100 mg twice daily (bid) continuously	Drug: acalabrutinib; Other Names: ACP-196
Experimental: Cohort 2 Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Drug: acalabrutinib; Other Names: ACP-196

Outcome Measures

Primary Outcome Measures

1. Safety Profile of Acalabrutinib With and Without Dexamethasone [From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression.]

   AEs and SAEs were coded by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA) reporting system. All AEs summarized were treatment-emergent. Summaries were also presented by the severity of the AE (per Common Toxicity Criteria for Adverse Events [CTCAE]) and by relationship to study drug as assessed by the investigator. Events of clinical interest (ECIs) selected for dedicated analysis were evaluated using Standardized MedDRA Queries, where available, by SOC, or by Sponsor-defined baskets of MedDRA Adverse Event Grouped Terms (AEGTs). The following ECIs were summarized: Cardiac events (including a subset of atrial fibrillation), cytopenias (anemia, leukopenia, neutropenia, and thrombocytopenia), hemorrhage (including a subset of major hemorrhage), hepatic events, hypertension, infection, interstitial lung disease/pneumonitis, second primary malignancies (second primary malignancies excluding skin), tumor lysis syndrome.

Secondary Outcome Measures

1. Pharmacokinetic (PK) Parameters Calculated for Acalabrutinib: AUC0-4, AUClast, AUCINF, Cmax, Tmax, λz, t1/2, CL/F, and Vz/F. PK Parameters Calculated for Dexamethasone: Tmax, Cmax, AUC0-4 and AUClast. [On Days 1 and 22: pre-dose, and at 0.5, 0.75, 1, 2, 4, and 6 hours after the morning dose. On Days 8, 15, and 28: pre-dose and 1 hour after the morning dose.]

   The plasma PK of study drug was characterized using noncompartmental analysis. PK parameters were calculated whenever possible, from plasma concentrations of acalabrutinib. Missing dates or times could have been imputed for PK and pharmacodynamic (PD) samples if the missing values could be established with an acceptable level of accuracy based on other information obtained during the visit in question. If PK and PD sampling for a 33 Final Clinical Study Report Drug Substance Acalabrutinib Study Code ACE-MY-001 Edition Number 2 Date 31 October 2018 given subject was not performed according to protocol, the subject could have been excluded from the PK and PD analyses. The PK parameters were tabulated and summarized using descriptive statistics. For each PD variable, the concentration at each assessment was described. The change from baseline to each assessment was summarized. As appropriate the on treatment values were compared with the pretreatment baseline values using paired t-tests.

2. Bruton Tyrosine Kinase (BTK) Occupancy [On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only.]

   The percent occupied BTK was calculated in each subject's peripheral blood mononuclear cells (PBMC) sample for each assessment timepoint using an ELISA-based method. Samples from 17 subjects met the criteria for data inclusion, having a dynamic range (signal to noise) of ≥5 for the Day 1 pre-dose timepoint. Acalabrutinib administered at 100 mg bid resulted in a median steady-state (Day 8) BTK target occupancy level of 95% and 98% for Cohort 1 and Cohort 2, respectively. The Days 28 and 56 assessments, both taken at pre-dose, were >97% occupancy for each cohort. Intersubject variability was low, with 6 of 7 (86%) subjects in Cohort 1 and 4 of 5 (80%) subjects in Cohort 2 having >90% BTK occupancy at steady-state trough (12h post-dose). The single subject in Cohort 2 with <90% occupancy at Day 8 pre-dose did not take their Day 7 doses.

3. Response Assessed According to Guidelines Proposed by the International Myeloma Workshop Consensus Panel and European Group for Blood and Marrow Transplant [From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression]

   Per EBMT: CR, negative immunofixation of serum and urine, disappearance of plasmacytomas and < 5% plasma cells; Stringent complete response (SCR), CR + normal flow cytometry and absence of clonal plasma cells; Very good partial response (VGPR), Serum and urine M-protein detectable on immunofixation but not on electrophoresis or > 90% reduction is serum and urine M protein; Partial response (PR), > 50% reduction in serum M-protein and > 90% reduction in 24 hour urine M-protein, > 50% reduction in baseline soft tissue plasmacytoma; Minimal response (MR), 25-49% reduction of serum M-protein and 50-59% reduction in 24 hour urine M-protein, 25-49% reduction in plasmacytomas and no increase in lytic bone lesions; Stable disease (SD), not meeting criteria for CR, VGPR, MR, PR or progressive disease (PD); PD, increase of 25% or more from nadir in serum M-protein, urine M-protein, new or increased bone lesions or plasmacytomas, or hypercalcemia solely attributed to multiple myeloma.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women ≥ 18 years of age.

• A confirmed diagnosis of MM, which has relapsed after, or been refractory to ≥ 1 prior therapy for MM, and is progressing at the time of study entry.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

• Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.

Exclusion Criteria:

• A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk

• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification

• Malabsorption syndrome, disease significantly affecting gastrointestinal function, gastric bypass, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

• Breast feeding or pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Baltimore	Maryland	United States
2	United Kingdom	Leicester		United Kingdom
3	Guys and St Thomas' Hospital NHS Foundation Trust	London		United Kingdom

Sponsors and Collaborators

• Acerta Pharma BV
• Acerta Pharma, LLC

Investigators

• Study Director: Acerta Clinical Trials, 1-888-292-9613

Study Documents (Full-Text)

• Study Protocol - Jan 13, 2016
• Statistical Analysis Plan - Sep 20, 2018

More Information

Publications

None provided.

• Responsible Party: Acerta Pharma BV
• ClinicalTrials.gov Identifier: NCT02211014
• Other Study ID Numbers: ACE-MY-001
• First Posted: Aug 7, 2014
• Last Update Posted: Jul 31, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Acerta Pharma BV: Bruton tyrosine kinase inhibitor; Btk; Multiple Myeloma; MM; ACP-196; acalabrutinib; Calquence
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Acalabrutinib

Study Results

Participant Flow

Recruitment Details	Multicenter, open-label, randomized, parallel-group study to evaluate the safety, pharmacokinetics, pharmacodynamics and activity of acalabrutinib with/without dexamethasone in subjects with relapsed/refractory multiple myeloma in US and United Kingdom. 27 subjects enrolled into 2 cohorts. Enrollment was discontinued because of lack of efficacy.

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
Period Title: Overall Study
STARTED	13	14
COMPLETED	11	8
NOT COMPLETED	2	6

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Total of all reporting groups
Overall Participants	13	14	27
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 69.2%	4 28.6%	13 48.1%
>=65 years	4 30.8%	10 71.4%	14 51.9%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60.0	68.5	65.0
Sex: Female, Male (Count of Participants)
Female	6 46.2%	4 28.6%	10 37%
Male	7 53.8%	10 71.4%	17 63%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%	0 0%	1 3.7%
Not Hispanic or Latino	11 84.6%	14 100%	25 92.6%
Unknown or Not Reported	1 7.7%	0 0%	1 3.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 7.1%	1 3.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 7.7%	4 28.6%	5 18.5%
White	11 84.6%	9 64.3%	20 74.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 7.7%	0 0%	1 3.7%
Region of Enrollment (participants) [Number]
United States	6 46.2%	7 50%	13 48.1%
United Kingdom	7 53.8%	7 50%	14 51.9%

Outcome Measures

1. Primary Outcome

Title	Safety Profile of Acalabrutinib With and Without Dexamethasone
Description	AEs and SAEs were coded by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA) reporting system. All AEs summarized were treatment-emergent. Summaries were also presented by the severity of the AE (per Common Toxicity Criteria for Adverse Events [CTCAE]) and by relationship to study drug as assessed by the investigator. Events of clinical interest (ECIs) selected for dedicated analysis were evaluated using Standardized MedDRA Queries, where available, by SOC, or by Sponsor-defined baskets of MedDRA Adverse Event Grouped Terms (AEGTs). The following ECIs were summarized: Cardiac events (including a subset of atrial fibrillation), cytopenias (anemia, leukopenia, neutropenia, and thrombocytopenia), hemorrhage (including a subset of major hemorrhage), hepatic events, hypertension, infection, interstitial lung disease/pneumonitis, second primary malignancies (second primary malignancies excluding skin), tumor lysis syndrome.
Time Frame	From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
Measure Participants	13	14
Treatment-emergent adverse events (TEAE)	13 100%	14 100%
Treatment-related TEAE	7 53.8%	7 50%
SAE	5 38.5%	9 64.3%
Treatment-related SAE	1 7.7%	2 14.3%
TEAE leading to actions taken on study drug	1 7.7%	8 57.1%

2. Secondary Outcome

Title	Pharmacokinetic (PK) Parameters Calculated for Acalabrutinib: AUC0-4, AUClast, AUCINF, Cmax, Tmax, λz, t1/2, CL/F, and Vz/F. PK Parameters Calculated for Dexamethasone: Tmax, Cmax, AUC0-4 and AUClast.
Description	The plasma PK of study drug was characterized using noncompartmental analysis. PK parameters were calculated whenever possible, from plasma concentrations of acalabrutinib. Missing dates or times could have been imputed for PK and pharmacodynamic (PD) samples if the missing values could be established with an acceptable level of accuracy based on other information obtained during the visit in question. If PK and PD sampling for a 33 Final Clinical Study Report Drug Substance Acalabrutinib Study Code ACE-MY-001 Edition Number 2 Date 31 October 2018 given subject was not performed according to protocol, the subject could have been excluded from the PK and PD analyses. The PK parameters were tabulated and summarized using descriptive statistics. For each PD variable, the concentration at each assessment was described. The change from baseline to each assessment was summarized. As appropriate the on treatment values were compared with the pretreatment baseline values using paired t-tests.
Time Frame	On Days 1 and 22: pre-dose, and at 0.5, 0.75, 1, 2, 4, and 6 hours after the morning dose. On Days 8, 15, and 28: pre-dose and 1 hour after the morning dose.

Outcome Measure Data

Analysis Population Description

Day 1: 24 (of 27 subjects enrolled) were equally randomized (1:1 ratio) into two cohorts to receive Acalabrutinib (12 in Cohort 1), or with dexamethasone (12 in Cohort 2). Day 22: 17 (of 24) subjects with PK data were remaining: 9 in Cohort 1 and 8 in Cohort 2. Seven subjects discontinued the study prior to Day 22.

Arm/Group Title	Cohort 1 - Day 1	Cohort 2 - Day 1	Cohort 1 - Day 22	Cohort 2 - Day 22
Arm/Group Description	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
Measure Participants	12	12	9	8
Cmax (ng/mL) - the maximum concentration observed	524 (112)	437 (91.5)	271 (103)	607 (90.8)
AUC (area under the curve)_0-4 (hr*ng/mL)	604 (72.9)	621 (64)	390 (105)	766 (60.5)
AUC_last (hr*ng/mL)	638 (69.5)	675 (56.9)	423 (102)	812 (58.3)
AUC_INF (infinity) (hr*ng/mL)	754 (67.8)	732 (63.1)	411 (111)	826 (62.6)

3. Secondary Outcome

Title	Bruton Tyrosine Kinase (BTK) Occupancy
Description	The percent occupied BTK was calculated in each subject's peripheral blood mononuclear cells (PBMC) sample for each assessment timepoint using an ELISA-based method. Samples from 17 subjects met the criteria for data inclusion, having a dynamic range (signal to noise) of ≥5 for the Day 1 pre-dose timepoint. Acalabrutinib administered at 100 mg bid resulted in a median steady-state (Day 8) BTK target occupancy level of 95% and 98% for Cohort 1 and Cohort 2, respectively. The Days 28 and 56 assessments, both taken at pre-dose, were >97% occupancy for each cohort. Intersubject variability was low, with 6 of 7 (86%) subjects in Cohort 1 and 4 of 5 (80%) subjects in Cohort 2 having >90% BTK occupancy at steady-state trough (12h post-dose). The single subject in Cohort 2 with <90% occupancy at Day 8 pre-dose did not take their Day 7 doses.
Time Frame	On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only.

Outcome Measure Data

Analysis Population Description

17 (of 27) subjects with evaluable data. For 10 subjects the data was excluded due to: no Day 1 sample received, low cells events or parent populations, or other deviation. Day 1 post and additional time points, further decrease of evaluable data due to: subject discontinuation, low cells events or parent populations, or other deviation.

Arm/Group Title	Cohort 1 - Day 1 Pre	Cohort 2 - Day 1 Pre	Cohort 1 - Day 1 Post	Cohort 2 - Day 1 Post	Cohort 1 - Day 8 Pre	Cohort 2 - Day 8 Pre	Cohort 1 - Day 8 Post	Cohort 2 - Day 8 Post	Cohort 1 - Day 28 Pre	Cohort 2 - Day 28 Pre	Cohort 1 - Day 56 Pre	Cohort 2 - Day 56 Pre
Arm/Group Description	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
Measure Participants	9	8	8	8	7	5	7	6	7	6	5	4
Mean (Standard Deviation) [percentage of occupied BTK]	0 (0)	0 (0)	98.5 (0.9)	98.5 (1.3)	93.2 (6.6)	94.3 (8.8)	98.6 (1.1)	96.8 (4.8)	97.6 (1.8)	95.8 (5.5)	95.7 (6.2)	97.6 (1.3)

4. Secondary Outcome

Title	Response Assessed According to Guidelines Proposed by the International Myeloma Workshop Consensus Panel and European Group for Blood and Marrow Transplant
Description	Per EBMT: CR, negative immunofixation of serum and urine, disappearance of plasmacytomas and < 5% plasma cells; Stringent complete response (SCR), CR + normal flow cytometry and absence of clonal plasma cells; Very good partial response (VGPR), Serum and urine M-protein detectable on immunofixation but not on electrophoresis or > 90% reduction is serum and urine M protein; Partial response (PR), > 50% reduction in serum M-protein and > 90% reduction in 24 hour urine M-protein, > 50% reduction in baseline soft tissue plasmacytoma; Minimal response (MR), 25-49% reduction of serum M-protein and 50-59% reduction in 24 hour urine M-protein, 25-49% reduction in plasmacytomas and no increase in lytic bone lesions; Stable disease (SD), not meeting criteria for CR, VGPR, MR, PR or progressive disease (PD); PD, increase of 25% or more from nadir in serum M-protein, urine M-protein, new or increased bone lesions or plasmacytomas, or hypercalcemia solely attributed to multiple myeloma.
Time Frame	From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Acalabrutinib 100 mg twice daily (bid) continuously	Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
Measure Participants	13	14
sCR	0 0%	0 0%
CR	0 0%	0 0%
VGPR	0 0%	0 0%
PR	0 0%	0 0%
MR	1 7.7%	2 14.3%
SD	5 38.5%	6 42.9%
PD	4 30.8%	1 7.1%
NE (not evaluable)	3 23.1%	5 35.7%

Adverse Events

Time Frame	Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 1210.
Arm/Group Title	Cohort 1		Cohort 2
Arm/Group Description	Acalabrutinib 100 mg twice daily (bid) continuously		Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
All Cause Mortality
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		4/14 (28.6%)
Serious Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/13 (38.5%)		9/14 (64.3%)
Blood and lymphatic system disorders
Hyperviscosity syndrome	1/13 (7.7%)		0/14 (0%)
Cardiac disorders
Angina pectoris	0/13 (0%)		1/14 (7.1%)
Gastrointestinal disorders
Lower gastrointestinal haemorrhage	0/13 (0%)		1/14 (7.1%)
General disorders
Fatigue	0/13 (0%)		1/14 (7.1%)
Pain	1/13 (7.7%)		0/14 (0%)
Infections and infestations
Bacteraemia	0/13 (0%)		1/14 (7.1%)
Cellulitis	0/13 (0%)		1/14 (7.1%)
Pneumonia	0/13 (0%)		1/14 (7.1%)
Pneumonia influenzal	0/13 (0%)		1/14 (7.1%)
Sepsis	1/13 (7.7%)		0/14 (0%)
Urinary tract infection	1/13 (7.7%)		0/14 (0%)
Investigations
Norovirus test positive	0/13 (0%)		1/14 (7.1%)
Metabolism and nutrition disorders
Hypercalcaemia	1/13 (7.7%)		1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/13 (7.7%)		0/14 (0%)
Nervous system disorders
Headache	0/13 (0%)		1/14 (7.1%)
Syncope	0/13 (0%)		1/14 (7.1%)
Renal and urinary disorders
Acute kidney injury	0/13 (0%)		1/14 (7.1%)
Renail impairment	0/13 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Skin mass	1/13 (7.7%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		14/14 (100%)
Blood and lymphatic system disorders
Anaemia	7/13 (53.8%)		6/14 (42.9%)
Thrombocytopenia	3/13 (23.1%)		0/14 (0%)
Ear and labyrinth disorders
Ear pain	1/13 (7.7%)		1/14 (7.1%)
Gastrointestinal disorders
Diarrhoea	6/13 (46.2%)		6/14 (42.9%)
Nausea	3/13 (23.1%)		3/14 (21.4%)
Constipation	1/13 (7.7%)		2/14 (14.3%)
Vomiting	2/13 (15.4%)		1/14 (7.1%)
Abdominal distension	1/13 (7.7%)		1/14 (7.1%)
Dyspepsia	0/13 (0%)		2/14 (14.3%)
General disorders
Fatigue	4/13 (30.8%)		2/14 (14.3%)
Pyrexia	0/13 (0%)		2/14 (14.3%)
Oedema peripheral	0/13 (0%)		2/14 (14.3%)
Pain	2/13 (15.4%)		0/14 (0%)
Infections and infestations
Rhinitis	1/13 (7.7%)		2/14 (14.3%)
Upper respiratory tract infection	1/13 (7.7%)		2/14 (14.3%)
Lower respiratory tract infection	2/13 (15.4%)		0/14 (0%)
Sepsis	1/13 (7.7%)		1/14 (7.1%)
Investigations
Cardiac murmur	1/13 (7.7%)		1/14 (7.1%)
Platelet count decreased	1/13 (7.7%)		1/14 (7.1%)
White blood cell count decreased	1/13 (7.7%)		1/14 (7.1%)
Metabolism and nutrition disorders
Decreased appetite	1/13 (7.7%)		2/14 (14.3%)
Hypercalcaemia	2/13 (15.4%)		1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Back pain	1/13 (7.7%)		4/14 (28.6%)
Pain in extremity	1/13 (7.7%)		2/14 (14.3%)
Arthralgia	0/13 (0%)		2/14 (14.3%)
Muscular weakness	1/13 (7.7%)		1/14 (7.1%)
Musculoskeletal chest pain	1/13 (7.7%)		1/14 (7.1%)
Musculoskeletal pain	2/13 (15.4%)		0/14 (0%)
Nervous system disorders
Headache	6/13 (46.2%)		4/14 (28.6%)
Dizziness	0/13 (0%)		2/14 (14.3%)
Lethargy	1/13 (7.7%)		1/14 (7.1%)
Psychiatric disorders
Confusional state	2/13 (15.4%)		2/14 (14.3%)
Contusion	3/13 (23.1%)		1/14 (7.1%)
Insomnia	0/13 (0%)		2/14 (14.3%)
Renal and urinary disorders
Acute kidney injury	0/13 (0%)		2/14 (14.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/13 (38.5%)		4/14 (28.6%)
Cough	4/13 (30.8%)		0/14 (0%)
Epistaxis	3/13 (23.1%)		1/14 (7.1%)
Haemoptysis	1/13 (7.7%)		1/14 (7.1%)
Nasal congestion	2/13 (15.4%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Site and PI can publish/publicly present the results of the study only with prior written consent of Sponsor or otherwise after expiry of 12 months following completion of the study. Site and PI agree to provide 30 days written notice to Sponsor prior to submission for publication or presentation."