Acalabrutinib in Patients With Relapsed/Refractory and Treatment naïve Deletion 17p CLL/SLL

Sponsor
Acerta Pharma BV (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02337829
Collaborator
National Institutes of Health (NIH) (NIH)
48
1
2
131.6
0.4

Study Details

Study Description

Brief Summary

This study is to determine the response to acalabrutinib in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Condition or Disease Intervention/Treatment Phase
  • Drug: Acalabrutinib (Arm A)
  • Drug: Acalabrutinib (Arm B)
Phase 2

Detailed Description

To investigate the safety and efficacy of acalabrutinib for patients with CLL/SLL that have relapsed/refractory disease or treatment naive deletion 17p.

Study Design

Study Type:
Interventional
Actual Enrollment :
48 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study Using ACP-196 (Acalabrutinib) in Patients With Relapsed/Refractory and Treatment-naïve Deletion 17p CLL/SLL: Pharmacodynamic Assessment of BTK Inhibition and Antitumor Response.
Actual Study Start Date :
Jan 12, 2015
Actual Primary Completion Date :
Jun 26, 2020
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.

Drug: Acalabrutinib (Arm A)
A1a) acalabrutinib, dose A daily: biopsy (T) schedule W; A1b) acalabrutinib, dose A daily: biopsy (T) schedule V. A2a) acalabrutinib, dose B q 12 hours: biopsy (T) schedule Y; A2b) acalabrutinib, dose B q 12 hours; biopsy (T) schedule Z
Other Names:
  • ACP-196
  • Drug: Acalabrutinib (Arm B)
    B1c) acalabrutinib, dose A daily: biopsy (U) schedule W; • B2c) acalabrutinib, dose B q12 hours: biopsy (U)) schedule Y.
    Other Names:
  • ACP-196
  • Experimental: Arm B

    Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.

    Drug: Acalabrutinib (Arm A)
    A1a) acalabrutinib, dose A daily: biopsy (T) schedule W; A1b) acalabrutinib, dose A daily: biopsy (T) schedule V. A2a) acalabrutinib, dose B q 12 hours: biopsy (T) schedule Y; A2b) acalabrutinib, dose B q 12 hours; biopsy (T) schedule Z
    Other Names:
  • ACP-196
  • Drug: Acalabrutinib (Arm B)
    B1c) acalabrutinib, dose A daily: biopsy (U) schedule W; • B2c) acalabrutinib, dose B q12 hours: biopsy (U)) schedule Y.
    Other Names:
  • ACP-196
  • Outcome Measures

    Primary Outcome Measures

    1. Response Based on Overall Response Rate [Cycle 1 (28 Days) to 6 months]

      The best response to treatment was determined according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria incorporating 2012 and 2013 clarifications pertaining to subjects treated with kinase inhibitors. Overall response rate (ORR) was the proportion of subjects who achieved complete response (CR), CR with incomplete marrow recovery (CRi), or partial response (PR) while on treatment before the initiation of new anti-cancer therapy or stem cell transplant.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Men and women 18 years of age and older with histologically confirmed disease.

    • Active disease as defined by at least one of the following (IWCLL consensus criteria):

    • Weight loss ≥10% within the previous 6 months

    • Extreme fatigue

    • Fevers of greater than 100.5ºF for ≥2 weeks without evidence of infection

    • Night sweats for more than one month without evidence of infection

    • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia

    • Massive or progressive splenomegaly

    • Massive nodes or clusters or progressive lymphadenopathy

    • Progressive lymphocytosis with an increase of >50% over a 2 month period, or an anticipated doubling time of less than 6 months

    • Compensated autoimmune hemolysis

    • Relapsed/Refractory CLL or treatment naïve CLL patients with 17p deletion, TP53 mutation, or NOTCH1 mutation

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

    • Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty and serial biopsies.

    • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).

    Exclusion Criteria:
    • Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or investigational products in the last 4 weeks.

    • Richter's transformation. Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy. Impaired hepatic function

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • Acerta Pharma BV
    • National Institutes of Health (NIH)

    Investigators

    • Study Director: AstraZeneca Clinical Study Information Center, 1-877-240-9479 - information.center@astrazeneca.com

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT02337829
    Other Study ID Numbers:
    • 15-H-0016
    First Posted:
    Jan 14, 2015
    Last Update Posted:
    Jul 14, 2022
    Last Verified:
    Jul 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Acalabrutinib 100 mg BID Relapse/Refractory Acalabrutinib 200 mg QD Relapse/Refractory Acalabrutinib 100 mg BID Treatment Naive Acalabrutinib 200 mg QD Treatment Naive
    Arm/Group Description relapsed/refractory subjects treated with acalabrutinib 100 mg twice a day Relapse/Refractory subjects treated with acalabrutinib 200 mg once a day Treatment naive subjects treated with acalabrutinib 100 mg twice a day Treatment naive subjects treated with acalabrutinib 200 mg once a day
    Period Title: Overall Study
    STARTED 18 14 6 10
    COMPLETED 0 0 0 0
    NOT COMPLETED 18 14 6 10

    Baseline Characteristics

    Arm/Group Title Acalabrutinib 100 mg BID Relapse/Refractory Acalabrutinib 200 mg QD Relapse/Refractory Acalabrutinib 100 mg BID Treatment Naive Acalabrutinib 200 mg QD Treatment Naive Total
    Arm/Group Description relapsed/refractory subjects treated with acalabrutinib 100 mg twice a day Relapse/Refractory subjects treated with acalabrutinib 200 mg once a day Treatment naive subjects treated with acalabrutinib 100 mg twice a day Treatment naive subjects treated with acalabrutinib 200 mg once a day Total of all reporting groups
    Overall Participants 18 14 6 10 48
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    63.3
    (9.3)
    62.3
    (7.7)
    68.3
    (10.9)
    62.1
    (8.7)
    63.4
    (8.9)
    Sex: Female, Male (Count of Participants)
    Female
    6
    33.3%
    3
    21.4%
    2
    33.3%
    4
    40%
    15
    31.3%
    Male
    12
    66.7%
    11
    78.6%
    4
    66.7%
    6
    60%
    33
    68.8%
    Race/Ethnicity, Customized (Number) [Number]
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    1
    2.1%
    Not Hispanic or Latino
    18
    100%
    14
    100%
    6
    100%
    9
    90%
    47
    97.9%
    Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Number) [Number]
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    2
    14.3%
    0
    0%
    0
    0%
    2
    4.2%
    Black or African American
    2
    11.1%
    0
    0%
    2
    33.3%
    1
    10%
    5
    10.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    16
    88.9%
    12
    85.7%
    4
    66.7%
    7
    70%
    39
    81.3%
    Not Reported
    0
    0%
    0
    0%
    0
    0%
    2
    20%
    2
    4.2%
    Region of Enrollment (Number) [Number]
    United States
    18
    100%
    14
    100%
    6
    100%
    10
    100%
    48
    100%

    Outcome Measures

    1. Primary Outcome
    Title Response Based on Overall Response Rate
    Description The best response to treatment was determined according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria incorporating 2012 and 2013 clarifications pertaining to subjects treated with kinase inhibitors. Overall response rate (ORR) was the proportion of subjects who achieved complete response (CR), CR with incomplete marrow recovery (CRi), or partial response (PR) while on treatment before the initiation of new anti-cancer therapy or stem cell transplant.
    Time Frame Cycle 1 (28 Days) to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Acalabrutinib 100 mg BID Relapse/Refractory Acalabrutinib 200 mg QD Relapse/Refractory Total Relapse/Refractory Subjects Acalabrutinib 100 mg BID Treatment Naive Acalabrutinib 200 mg QD Treatment Naive Total Treatment Naive Subjects
    Arm/Group Description relapsed/refractory subjects treated with acalabrutinib 100 mg twice a day Relapse/Refractory subjects treated with acalabrutinib 200 mg once a day All relapse/refractory subjects in both dose groups combined Treatment naive subjects treated with acalabrutinib 100 mg twice a day Treatment naive subjects treated with acalabrutinib 200 mg once a day All treatment naive subjects in both dose groups combined
    Measure Participants 18 13 31 6 10 16
    Count of Participants [Participants]
    17
    94.4%
    11
    78.6%
    28
    466.7%
    6
    60%
    8
    16.7%
    14
    NaN

    Adverse Events

    Time Frame From first dose of study drug until 30 days post last dose for each subject; an average of approximately 38 months.
    Adverse Event Reporting Description
    Arm/Group Title Acalabrutinib 100 mg BID Relapse/Refractory Acalabrutinib 200 mg QD Relapse/Refractory Acalabrutinib 100 mg BID Treatment Naive Acalabrutinib 200 mg QD Treatment Naive
    Arm/Group Description relapsed/refractory subjects treated with acalabrutinib 100 mg twice a day Relapse/Refractory subjects treated with acalabrutinib 200 mg once a day Treatment naive subjects treated with acalabrutinib 100 mg twice a day Treatment naive subjects treated with acalabrutinib 200 mg once a day
    All Cause Mortality
    Acalabrutinib 100 mg BID Relapse/Refractory Acalabrutinib 200 mg QD Relapse/Refractory Acalabrutinib 100 mg BID Treatment Naive Acalabrutinib 200 mg QD Treatment Naive
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/18 (0%) 1/14 (7.1%) 0/6 (0%) 0/10 (0%)
    Serious Adverse Events
    Acalabrutinib 100 mg BID Relapse/Refractory Acalabrutinib 200 mg QD Relapse/Refractory Acalabrutinib 100 mg BID Treatment Naive Acalabrutinib 200 mg QD Treatment Naive
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/18 (61.1%) 8/14 (57.1%) 3/6 (50%) 5/10 (50%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Cardiac disorders
    Cardiac failure 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Left ventricular dysfunction 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Ear and labyrinth disorders
    Vertigo 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Diverticular perforation 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Enterocolitis 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Upper gastrointestinal haemorrhage 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    General disorders
    Non-cardiac chest pain 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Pyrexia 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Hepatic failure 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Infections and infestations
    Diverticulitis 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 2
    Hepatitis b reactivation 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Lower respiratory tract infection fungal 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Pneumonia 2/18 (11.1%) 2 1/14 (7.1%) 2 0/6 (0%) 0 0/10 (0%) 0
    Pneumonia influenzal 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Skin infection 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Upper respiratory tract infection 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Musculoskeletal and connective tissue disorders
    Neck pain 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung adenocarcinoma 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Malignant melanoma 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Myelodysplastic syndrome 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Plasma cell myeloma 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Prostate cancer 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Prostate cancer metastatic 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Renal cell carcinoma 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Squamous cell carcinoma 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Nervous system disorders
    Headache 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Syncope 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleuritic pain 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Vascular disorders
    Haematoma 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Hypotension 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Other (Not Including Serious) Adverse Events
    Acalabrutinib 100 mg BID Relapse/Refractory Acalabrutinib 200 mg QD Relapse/Refractory Acalabrutinib 100 mg BID Treatment Naive Acalabrutinib 200 mg QD Treatment Naive
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 18/18 (100%) 14/14 (100%) 6/6 (100%) 10/10 (100%)
    Blood and lymphatic system disorders
    Anaemia 2/18 (11.1%) 2 1/14 (7.1%) 1 3/6 (50%) 4 1/10 (10%) 1
    Autoimmune haemolytic anaemia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Febrile neutropenia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hyperglobulinaemia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Increased tendency to bruise 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Lymph node pain 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Polycythaemia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Splenomegaly 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Cardiac disorders
    Angina pectoris 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Aortic valve disease 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Aortic valve incompetence 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Arrhythmia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Atrial flutter 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Atrioventricular block first degree 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Bradycardia 0/18 (0%) 0 1/14 (7.1%) 3 0/6 (0%) 0 0/10 (0%) 0
    Cardiac failure 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 2 0/10 (0%) 0
    Cardiomegaly 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Coronary artery disease 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Palpitations 2/18 (11.1%) 3 3/14 (21.4%) 3 1/6 (16.7%) 1 2/10 (20%) 3
    Pericardial effusion 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Pericarditis 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Pulmonary valve disease 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Sinus bradycardia 2/18 (11.1%) 2 1/14 (7.1%) 1 1/6 (16.7%) 1 2/10 (20%) 2
    Sinus tachycardia 1/18 (5.6%) 1 2/14 (14.3%) 3 1/6 (16.7%) 1 1/10 (10%) 1
    Supraventricular tachycardia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Ventricular arrhythmia 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Ventricular extrasystoles 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Ear and labyrinth disorders
    Ear congestion 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Ear discomfort 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Ear pruritus 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    External ear inflammation 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hypoacusis 0/18 (0%) 0 2/14 (14.3%) 3 0/6 (0%) 0 0/10 (0%) 0
    Middle ear inflammation 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Tinnitus 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Vertigo 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Endocrine disorders
    Adrenal mass 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hypothyroidism 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Thyroid mass 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Eye disorders
    Age-related macular degeneration 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Asthenopia 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Blepharospasm 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Cataract 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Conjunctival haemorrhage 1/18 (5.6%) 1 1/14 (7.1%) 1 2/6 (33.3%) 2 0/10 (0%) 0
    Conjunctival hyperaemia 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Dry eye 0/18 (0%) 0 1/14 (7.1%) 1 2/6 (33.3%) 2 1/10 (10%) 1
    Eye haemorrhage 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Eye pain 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Keratitis 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Lacrimation increased 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Lenticular opacities 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Ocular hypertension 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Photophobia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Retinal tear 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 2 0/10 (0%) 0
    Uveitis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Vision blurred 1/18 (5.6%) 1 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Vitreous floaters 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 3/10 (30%) 3
    Vitreous haemorrhage 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Abdominal distension 1/18 (5.6%) 1 2/14 (14.3%) 2 2/6 (33.3%) 3 1/10 (10%) 1
    Abdominal hernia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Abdominal pain 2/18 (11.1%) 3 2/14 (14.3%) 2 0/6 (0%) 0 2/10 (20%) 2
    Abdominal pain upper 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Anal fissure 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Anal incontinence 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Colitis 0/18 (0%) 0 1/14 (7.1%) 3 0/6 (0%) 0 1/10 (10%) 1
    Constipation 3/18 (16.7%) 4 1/14 (7.1%) 2 0/6 (0%) 0 1/10 (10%) 2
    Dental caries 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 1/10 (10%) 1
    Diarrhoea 7/18 (38.9%) 12 7/14 (50%) 13 4/6 (66.7%) 5 4/10 (40%) 9
    Dry mouth 0/18 (0%) 0 1/14 (7.1%) 1 2/6 (33.3%) 2 0/10 (0%) 0
    Dyspepsia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 4/10 (40%) 5
    Dysphagia 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 1/10 (10%) 1
    Flatulence 2/18 (11.1%) 2 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Food poisoning 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Frequent bowel movements 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Gastritis 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Gastrointestinal disorder 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Gastrointestinal sounds abnormal 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Gastrooesophageal reflux disease 1/18 (5.6%) 1 2/14 (14.3%) 2 1/6 (16.7%) 1 1/10 (10%) 1
    Haemorrhoidal haemorrhage 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Haemorrhoids 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Intestinal perforation 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Large intestine polyp 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Mouth haemorrhage 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Nausea 5/18 (27.8%) 8 6/14 (42.9%) 7 2/6 (33.3%) 2 3/10 (30%) 7
    Oesophagitis 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Oral dysaesthesia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Poor dental condition 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Rectal haemorrhage 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Retching 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Stomatitis 3/18 (16.7%) 3 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Tongue discolouration 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Toothache 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Umbilical hernia 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Vomiting 3/18 (16.7%) 3 5/14 (35.7%) 6 0/6 (0%) 0 2/10 (20%) 4
    General disorders
    Chest discomfort 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Chest pain 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Chills 2/18 (11.1%) 2 2/14 (14.3%) 2 1/6 (16.7%) 1 1/10 (10%) 1
    Cyst 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Facial pain 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Fatigue 4/18 (22.2%) 5 5/14 (35.7%) 6 4/6 (66.7%) 6 3/10 (30%) 4
    Feeling abnormal 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Hernia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Inflammation 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Influenza like illness 7/18 (38.9%) 14 9/14 (64.3%) 15 3/6 (50%) 6 8/10 (80%) 15
    Injection site bruising 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Injection site pain 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Injection site reaction 3/18 (16.7%) 3 1/14 (7.1%) 3 0/6 (0%) 0 3/10 (30%) 4
    Localised oedema 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 2 0/10 (0%) 0
    Non-cardiac chest pain 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Oedema 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Oedema peripheral 3/18 (16.7%) 3 4/14 (28.6%) 5 5/6 (83.3%) 7 2/10 (20%) 2
    Pain 0/18 (0%) 0 1/14 (7.1%) 2 2/6 (33.3%) 3 2/10 (20%) 2
    Pyrexia 4/18 (22.2%) 5 3/14 (21.4%) 3 0/6 (0%) 0 4/10 (40%) 9
    Hepatobiliary disorders
    Cholelithiasis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Dilatation intrahepatic duct acquired 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Hepatic mass 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Immune system disorders
    Allergy to arthropod sting 0/18 (0%) 0 2/14 (14.3%) 3 0/6 (0%) 0 0/10 (0%) 0
    Drug hypersensitivity 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Hypogammaglobulinaemia 0/18 (0%) 0 2/14 (14.3%) 2 2/6 (33.3%) 2 0/10 (0%) 0
    Seasonal allergy 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Infections and infestations
    Abscess oral 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Bacterial vaginosis 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Bronchitis 3/18 (16.7%) 4 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Cellulitis 2/18 (11.1%) 3 2/14 (14.3%) 3 0/6 (0%) 0 1/10 (10%) 1
    Chronic sinusitis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Clostridium difficile colitis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Conjunctivitis 1/18 (5.6%) 1 3/14 (21.4%) 3 1/6 (16.7%) 1 0/10 (0%) 0
    Cystitis 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Diverticulitis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Erythema migrans 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Eye infection 1/18 (5.6%) 1 1/14 (7.1%) 2 0/6 (0%) 0 0/10 (0%) 0
    Fungal skin infection 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Gastroenteritis viral 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Gingivitis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Herpes virus infection 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Herpes zoster 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Herpes zoster reactivation 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Laryngitis 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 2
    Lip infection 2/18 (11.1%) 2 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Localised infection 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Lyme disease 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Mucosal infection 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Mycobacterium avium complex infection 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Nasopharyngitis 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Onychomycosis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Oral candidiasis 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Oral herpes 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Otitis media 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Pneumocystis jirovecii pneumonia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Pneumonia 2/18 (11.1%) 2 2/14 (14.3%) 4 1/6 (16.7%) 1 3/10 (30%) 3
    Prostate infection 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Sinusitis 4/18 (22.2%) 8 3/14 (21.4%) 3 3/6 (50%) 4 1/10 (10%) 1
    Skin infection 3/18 (16.7%) 3 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Tinea versicolour 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Tooth infection 1/18 (5.6%) 1 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Upper respiratory tract infection 9/18 (50%) 13 6/14 (42.9%) 12 3/6 (50%) 4 5/10 (50%) 10
    Urinary tract infection 3/18 (16.7%) 7 3/14 (21.4%) 3 2/6 (33.3%) 2 1/10 (10%) 1
    Vaginal infection 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Varicella zoster virus infection 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Viral infection 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Viral upper respiratory tract infection 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Injury, poisoning and procedural complications
    Animal bite 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Arthropod bite 3/18 (16.7%) 4 2/14 (14.3%) 2 1/6 (16.7%) 1 1/10 (10%) 1
    Cartilage injury 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Contusion 11/18 (61.1%) 16 9/14 (64.3%) 14 6/6 (100%) 11 6/10 (60%) 12
    Epicondylitis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Fall 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Foot fracture 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hand fracture 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Infusion related reaction 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Ligament sprain 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Limb injury 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Mouth injury 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 2/10 (20%) 2
    Muscle strain 3/18 (16.7%) 3 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Post procedural contusion 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Post procedural haemorrhage 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Road traffic accident 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Skin abrasion 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Skin laceration 2/18 (11.1%) 2 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Spinal fracture 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Tooth fracture 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Investigations
    Alanine aminotransferase increased 2/18 (11.1%) 3 1/14 (7.1%) 1 1/6 (16.7%) 1 1/10 (10%) 1
    Aspartate aminotransferase increased 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 2/10 (20%) 2
    Beta 2 microglobulin increased 2/18 (11.1%) 2 1/14 (7.1%) 3 1/6 (16.7%) 3 0/10 (0%) 0
    Bilirubin conjugated increased 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Blood alkaline phosphatase 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Blood alkaline phosphatase increased 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Blood bilirubin increased 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Blood creatine phosphokinase increased 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Blood creatinine increased 3/18 (16.7%) 5 2/14 (14.3%) 2 0/6 (0%) 0 4/10 (40%) 7
    Blood lactate dehydrogenase increased 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 2 0/10 (0%) 0
    Blood urea decreased 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Blood urea increased 2/18 (11.1%) 2 2/14 (14.3%) 2 1/6 (16.7%) 1 3/10 (30%) 3
    C-reactive protein increased 1/18 (5.6%) 1 1/14 (7.1%) 1 2/6 (33.3%) 2 2/10 (20%) 2
    Cd4 lymphocytes decreased 6/18 (33.3%) 7 4/14 (28.6%) 8 3/6 (50%) 4 0/10 (0%) 0
    Cardiac murmur 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Ejection fraction decreased 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Electrocardiogram qt prolonged 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Fibrin d dimer increased 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Haemoglobin increased 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Haptoglobin decreased 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    International normalised ratio increased 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Lymphocyte count decreased 3/18 (16.7%) 8 3/14 (21.4%) 13 3/6 (50%) 10 0/10 (0%) 0
    Lymphocyte count increased 3/18 (16.7%) 4 3/14 (21.4%) 3 1/6 (16.7%) 1 0/10 (0%) 0
    Neutrophil count decreased 5/18 (27.8%) 6 6/14 (42.9%) 11 1/6 (16.7%) 1 1/10 (10%) 5
    Neutrophil count increased 2/18 (11.1%) 3 0/14 (0%) 0 0/6 (0%) 0 2/10 (20%) 2
    Platelet count decreased 4/18 (22.2%) 14 2/14 (14.3%) 2 2/6 (33.3%) 7 3/10 (30%) 5
    Platelet count increased 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Prostatic specific antigen increased 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Weight decreased 3/18 (16.7%) 4 4/14 (28.6%) 9 1/6 (16.7%) 2 2/10 (20%) 2
    Weight increased 5/18 (27.8%) 13 3/14 (21.4%) 9 4/6 (66.7%) 12 2/10 (20%) 4
    White blood cell count decreased 1/18 (5.6%) 3 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Hyperchloraemia 2/18 (11.1%) 3 3/14 (21.4%) 3 0/6 (0%) 0 1/10 (10%) 1
    Hyperglycaemia 7/18 (38.9%) 10 4/14 (28.6%) 8 3/6 (50%) 5 3/10 (30%) 3
    Hyperkalaemia 2/18 (11.1%) 3 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Hyperlipidaemia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hypermagnesaemia 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Hypernatraemia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hyperphosphataemia 1/18 (5.6%) 2 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Hyperuricaemia 0/18 (0%) 0 1/14 (7.1%) 1 2/6 (33.3%) 4 0/10 (0%) 0
    Hypoalbuminaemia 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Hypocalcaemia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hypochloraemia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Hypoglycaemia 1/18 (5.6%) 1 1/14 (7.1%) 1 1/6 (16.7%) 1 0/10 (0%) 0
    Hypokalaemia 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Hypophosphataemia 3/18 (16.7%) 4 3/14 (21.4%) 4 1/6 (16.7%) 1 0/10 (0%) 0
    Iron deficiency 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Obesity 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Type 2 diabetes mellitus 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/18 (33.3%) 7 5/14 (35.7%) 8 3/6 (50%) 7 5/10 (50%) 9
    Arthritis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Back pain 3/18 (16.7%) 3 0/14 (0%) 0 1/6 (16.7%) 3 1/10 (10%) 2
    Bone pain 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Coccydynia 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Flank pain 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Gouty arthritis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 2 0/10 (0%) 0
    Joint stiffness 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Joint swelling 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Limb mass 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Muscle spasms 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Musculoskeletal chest pain 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 2 1/10 (10%) 1
    Musculoskeletal pain 1/18 (5.6%) 1 3/14 (21.4%) 3 1/6 (16.7%) 1 1/10 (10%) 1
    Myalgia 8/18 (44.4%) 10 8/14 (57.1%) 13 1/6 (16.7%) 2 5/10 (50%) 7
    Neck pain 1/18 (5.6%) 1 3/14 (21.4%) 3 0/6 (0%) 0 1/10 (10%) 1
    Pain in extremity 3/18 (16.7%) 3 2/14 (14.3%) 2 5/6 (83.3%) 6 2/10 (20%) 2
    Pain in jaw 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Rotator cuff syndrome 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Spondylolisthesis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Trigger finger 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Dysplastic naevus 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Melanocytic naevus 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Papilloma 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Skin papilloma 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Squamous cell carcinoma 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Nervous system disorders
    Amnesia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Ataxia 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Carotid arteriosclerosis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Carotid artery stenosis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Cervical radiculopathy 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Dizziness 4/18 (22.2%) 7 5/14 (35.7%) 5 1/6 (16.7%) 1 3/10 (30%) 4
    Headache 12/18 (66.7%) 20 10/14 (71.4%) 15 5/6 (83.3%) 10 6/10 (60%) 11
    Hypoaesthesia 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Memory impairment 0/18 (0%) 0 1/14 (7.1%) 1 2/6 (33.3%) 2 1/10 (10%) 1
    Meralgia paraesthetica 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Neuralgia 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Paraesthesia 1/18 (5.6%) 1 1/14 (7.1%) 1 1/6 (16.7%) 1 2/10 (20%) 2
    Peripheral sensory neuropathy 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Presyncope 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Restless legs syndrome 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Syncope 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 3/10 (30%) 3
    Tremor 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Psychiatric disorders
    Anxiety 2/18 (11.1%) 2 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Depression 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Insomnia 5/18 (27.8%) 5 4/14 (28.6%) 5 0/6 (0%) 0 2/10 (20%) 3
    Phonophobia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Suicidal ideation 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Renal and urinary disorders
    Chromaturia 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Chronic kidney disease 3/18 (16.7%) 3 0/14 (0%) 0 1/6 (16.7%) 5 1/10 (10%) 1
    Haematuria 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Nocturia 2/18 (11.1%) 2 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Pollakiuria 3/18 (16.7%) 4 2/14 (14.3%) 2 3/6 (50%) 3 1/10 (10%) 2
    Renal cyst 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Renal cyst haemorrhage 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Renal mass 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Urinary incontinence 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Urinary tract obstruction 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Erectile dysfunction 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Hydrometra 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Pelvic fluid collection 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Prostatic obstruction 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Bronchostenosis 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Cough 9/18 (50%) 11 2/14 (14.3%) 2 3/6 (50%) 4 5/10 (50%) 6
    Dysphonia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Dyspnoea 3/18 (16.7%) 3 5/14 (35.7%) 7 3/6 (50%) 5 3/10 (30%) 4
    Epistaxis 2/18 (11.1%) 5 2/14 (14.3%) 3 0/6 (0%) 0 1/10 (10%) 3
    Laryngeal inflammation 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Lung infiltration 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Lung opacity 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Nasal congestion 6/18 (33.3%) 9 3/14 (21.4%) 3 2/6 (33.3%) 2 4/10 (40%) 4
    Nasal polyps 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Nasal septum deviation 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Oropharyngeal pain 3/18 (16.7%) 3 2/14 (14.3%) 2 2/6 (33.3%) 2 1/10 (10%) 1
    Pleural effusion 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Productive cough 2/18 (11.1%) 2 1/14 (7.1%) 1 2/6 (33.3%) 3 0/10 (0%) 0
    Pulmonary mass 4/18 (22.2%) 4 2/14 (14.3%) 2 3/6 (50%) 4 0/10 (0%) 0
    Rhinitis allergic 3/18 (16.7%) 3 2/14 (14.3%) 2 0/6 (0%) 0 0/10 (0%) 0
    Rhinorrhoea 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Sinus disorder 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Sinus pain 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Sleep apnoea syndrome 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Upper-airway cough syndrome 5/18 (27.8%) 5 1/14 (7.1%) 1 2/6 (33.3%) 2 0/10 (0%) 0
    Wheezing 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Skin and subcutaneous tissue disorders
    Actinic keratosis 2/18 (11.1%) 2 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Alopecia 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Blister 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Blood blister 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Dermal cyst 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Dermatitis bullous 0/18 (0%) 0 1/14 (7.1%) 1 1/6 (16.7%) 1 1/10 (10%) 1
    Dermatitis contact 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Dry skin 4/18 (22.2%) 4 3/14 (21.4%) 3 1/6 (16.7%) 1 1/10 (10%) 1
    Ecchymosis 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Erythema 1/18 (5.6%) 1 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Hyperhidrosis 1/18 (5.6%) 1 3/14 (21.4%) 3 1/6 (16.7%) 1 3/10 (30%) 4
    Hyperkeratosis 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 1/10 (10%) 1
    Nail ridging 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Night sweats 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Onychoclasis 3/18 (16.7%) 3 1/14 (7.1%) 1 1/6 (16.7%) 1 1/10 (10%) 1
    Pain of skin 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Petechiae 5/18 (27.8%) 5 4/14 (28.6%) 5 0/6 (0%) 0 5/10 (50%) 8
    Photosensitivity reaction 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Pruritus 2/18 (11.1%) 2 1/14 (7.1%) 1 0/6 (0%) 0 3/10 (30%) 4
    Psoriasis 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Purpura 2/18 (11.1%) 2 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Rash erythematous 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Rash maculo-papular 5/18 (27.8%) 7 8/14 (57.1%) 17 1/6 (16.7%) 1 4/10 (40%) 6
    Rosacea 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Seborrhoea 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Skin atrophy 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Skin exfoliation 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Skin haemorrhage 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Skin hyperpigmentation 1/18 (5.6%) 1 1/14 (7.1%) 2 0/6 (0%) 0 0/10 (0%) 0
    Skin hypopigmentation 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Skin lesion 2/18 (11.1%) 2 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Skin mass 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 1/10 (10%) 1
    Skin ulcer 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Telangiectasia 0/18 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/10 (0%) 0
    Urticaria 1/18 (5.6%) 1 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Vascular disorders
    Aortic aneurysm 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Aortic dilatation 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Fibromuscular dysplasia 1/18 (5.6%) 1 0/14 (0%) 0 0/6 (0%) 0 0/10 (0%) 0
    Flushing 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Haematoma 3/18 (16.7%) 3 2/14 (14.3%) 2 1/6 (16.7%) 2 0/10 (0%) 0
    Hot flush 1/18 (5.6%) 1 2/14 (14.3%) 2 0/6 (0%) 0 4/10 (40%) 4
    Hypertension 10/18 (55.6%) 32 7/14 (50%) 13 3/6 (50%) 8 2/10 (20%) 5
    Hypotension 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0
    Lymphoedema 0/18 (0%) 0 2/14 (14.3%) 2 0/6 (0%) 0 1/10 (10%) 1
    Subclavian artery occlusion 0/18 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/10 (10%) 1
    Venous thrombosis 0/18 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/10 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Acerta Clinical Trials
    Organization Acerta Pharma B.V.
    Phone 1-888-292-9613
    Email acertamc@dlss.com
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT02337829
    Other Study ID Numbers:
    • 15-H-0016
    First Posted:
    Jan 14, 2015
    Last Update Posted:
    Jul 14, 2022
    Last Verified:
    Jul 1, 2022