A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy

• Sponsor: Acerta Pharma BV (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02717611
• Collaborator: (none)
• Enrollment: 60
• Locations: 23
• Arm: 1
• Anticipated Duration (Months): 117.8
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

A Phase 2 Study to evaluate the Efficacy and Safety of ACP-196 (acalabrutinib) in Subjects with Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: ACP-196 (acalabrutinib)	Phase 2

Detailed Description

A Multicenter, Open-Label, Phase 2 study evaluating the efficacy and safety of Acalabrutinib in subjects with relapsed/refractory CLL (N=60) who are intolerant of ibrutinib therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Efficacy and Safety of ACP-196 in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy
• Actual Study Start Date: Mar 8, 2016
• Actual Primary Completion Date: Oct 16, 2020
• Anticipated Study Completion Date: Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ACP-196 (acalabrutinib) ACP-196 (acalabrutinib) 100 mg to be administered orally (PO) twice a day BID	Drug: ACP-196 (acalabrutinib); ACP-196 100 mg to be administered orally (PO) twice a day BID.; Other Names: Acalabrutinib

Outcome Measures

Primary Outcome Measures

1. The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) [From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 4 years and 7 months). 1 cycle = 28 days]

   The overall response rate (ORR) of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. ORR is defined as the proportion of subjects achieving a best overall response (BOR) of either complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) at or before initiation of subsequent anticancer therapy. ORR will be analyzed per investigator's assessment.

Secondary Outcome Measures

1. Progression-Free Survival [From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).]

   The progression-free survival of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. PFS is calculated as date of disease progression or death (censoring date for censored subjects) - first dose date + 1.

2. Duration of Response [From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)]

   The duration of response of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. DOR is calculated as date of disease progression or death (censoring date for censored subjects) - date of achieving the first CR, CRi, nPR, or PR + 1.

3. Time-to-Next Treatment [From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)]

   The time to next treatment of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. TTNT is defined as the time from date of first acalabrutinib treatment to date of institution of subsequent anticancer therapy for CLL or death due to any cause, whichever comes first. Subjects who do not have the above specified events prior to the data cutoff date will be censored at the date of last visit. TTNT will be calculated as follows: (Earlier date of institution of subsequent anticancer therapy for CLL or date of death due to any cause) - date of first dose + 1. For censored subjects, date of last visit will replace earlier date of use of subsequent anticancer therapy for CLL or date of death due to any cause in the calculation.

4. Overall Survival [From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).]

   The overall survival of ACP-319 (acalabrutinib) in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Men and women ≥ 18 years of age.

2. Prior diagnosis of CLL

3. Must have received ≥ 1 prior therapy for CLL

4. Intolerant of ibrutinib

5. Documented disease progression after stopping ibrutinib therapy as defined by the IWCLL 2008 criteria

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

7. ECOG performance status of ≤ 2.

Exclusion Criteria:

1. Ongoing AE attributed to ibrutinib therapy

2. Treatment with systemic anticancer therapy for CLL is prohibited between discontinuation of ibrutinib and enrollment on this trial.

3. Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT- 199)

4. Prior malignancy (other than CLL), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the subject has been disease free for ≥ 2 years.

5. Significant cardiovascular disease such as uncontrolled or symptomatic untreated 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, or QTc > 480 msec at screening. Exception:

Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.

1. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.

2. Evidence of active Richter's transformation or any evidence of disease progression on ibrutinib therapy or any BTK inhibitor.

3. CNS involvement by CLL or related Richter's transformation.

4. Known history of human immunodeficiency virus (HIV), serologic status reflecting active hepatitis B or C infection, or any uncontrolled active systemic infection.

5. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)

6. History of stroke or intracranial hemorrhage within 2 months before the first dose of study drug.

7. History of bleeding diathesis.

8. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.

9. Major surgical procedure within 28 days of first dose of study drug.

10. Requires treatment with a strong CYP3A inhibitor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tucson	Arizona	United States	85704
2	Research Site	Concord	California	United States	94520
3	Research Site	La Jolla	California	United States	92093
4	Research Site	Palo Alto	California	United States	94304
5	Research Site	Washington	District of Columbia	United States	20007
6	Research Site	Chicago	Illinois	United States	60611
7	Research Site	Lake Success	New York	United States	11042
8	Research Site	New York	New York	United States	10021
9	Research Site	Columbus	Ohio	United States	43210
10	Research Site	Nashville	Tennessee	United States	37203
11	Research Site	Houston	Texas	United States	77030
12	Research Site	Sherman	Texas	United States	USA
13	Research Site	Seattle	Washington	United States	98108
14	Research Site	Seattle	Washington	United States	98122
15	Research Site	Spokane	Washington	United States	99208
16	Research Site	Milwaukee	Wisconsin	United States	53226
17	Research Site	Brugge		Belgium	8000
18	Research Site	Bordeaux		France	33076, FR
19	Research Site	Haifa		Israel	31000
20	Research Site	Madrid		Spain	28006
21	Research Site	Bournemouth		United Kingdom	BH7 7DW
22	Research Site	Leeds		United Kingdom	LS9 7TF
23	Research Site	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• Acerta Pharma BV

Investigators

• Study Director: Acerta Clinical Trials, 1-888-292-9613; [e-mail]

Study Documents (Full-Text)

• Study Protocol - Jun 25, 2020
• Statistical Analysis Plan - Jun 12, 2020

More Information

Additional Information:

• redacted CSP
• redacted CSR Synopsis
• redacted SAP

Publications

None provided.

• Responsible Party: Acerta Pharma BV
• ClinicalTrials.gov Identifier: NCT02717611
• Other Study ID Numbers: ACE-CL-208
• First Posted: Mar 24, 2016
• Last Update Posted: May 20, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Acerta Pharma BV: Chronic Lymphocytic Leukemia; Ibrutinib Intolerant
• Additional relevant MeSH terms: Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Acalabrutinib

Study Results

Participant Flow

Pre-assignment Detail	For the ACE-CL-208 program, Study Terminated by Sponsor refers to the following: Patients receiving treatment benefits will continue to be provided with study medication in the Post Final Analysis Management of the trial. Sponsor has terminated further data collection for analysis and reporting

Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
Period Title: Overall Study
STARTED	60
COMPLETED	0
NOT COMPLETED	60

Baseline Characteristics

Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
Overall Participants	60
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	69.2 (9.4)
Sex: Female, Male (Count of Participants)
Female	22 36.7%
Male	38 63.3%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	2 3.3%
Not Hispanic or Latino	54 90%
Not Reported	4 6.7%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	0 0%
Asian	0 0%
Black or African American	1 1.7%
Native Hawaiian or Other Pacific Islander	0 0%
White	56 93.3%
Other	1 1.7%
Not Reported	2 3.3%
Region of Enrollment (Number) [Number]
United States	49 81.7%
Europe	11 18.3%

Outcome Measures

1. Primary Outcome

Title	The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib)
Description	The overall response rate (ORR) of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. ORR is defined as the proportion of subjects achieving a best overall response (BOR) of either complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) at or before initiation of subsequent anticancer therapy. ORR will be analyzed per investigator's assessment.
Time Frame	From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 4 years and 7 months). 1 cycle = 28 days

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
Measure Participants	60
Number (95% Confidence Interval) [Percentage of participants]	70.0 116.7%

2. Secondary Outcome

Title	Progression-Free Survival
Description	The progression-free survival of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. PFS is calculated as date of disease progression or death (censoring date for censored subjects) - first dose date + 1.
Time Frame	From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
Measure Participants	60
Median (95% Confidence Interval) [Months]	NA

3. Secondary Outcome

Title	Duration of Response
Description	The duration of response of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. DOR is calculated as date of disease progression or death (censoring date for censored subjects) - date of achieving the first CR, CRi, nPR, or PR + 1.
Time Frame	From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
Measure Participants	60
Median (95% Confidence Interval) [Months]	NA

4. Secondary Outcome

Title	Time-to-Next Treatment
Description	The time to next treatment of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. TTNT is defined as the time from date of first acalabrutinib treatment to date of institution of subsequent anticancer therapy for CLL or death due to any cause, whichever comes first. Subjects who do not have the above specified events prior to the data cutoff date will be censored at the date of last visit. TTNT will be calculated as follows: (Earlier date of institution of subsequent anticancer therapy for CLL or date of death due to any cause) - date of first dose + 1. For censored subjects, date of last visit will replace earlier date of use of subsequent anticancer therapy for CLL or date of death due to any cause in the calculation.
Time Frame	From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
Measure Participants	60
Median (95% Confidence Interval) [Months]	44.0

5. Secondary Outcome

Title	Overall Survival
Description	The overall survival of ACP-319 (acalabrutinib) in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy
Time Frame	From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
Measure Participants	60
Median (95% Confidence Interval) [Months]	NA

Adverse Events

Time Frame	From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Arm/Group Title	Acalabrutinib
Arm/Group Description	Acalabrutinib 100 mg BID
All Cause Mortality
	Acalabrutinib
	Affected / at Risk (%)	# Events
Total	13/60 (21.7%)
Serious Adverse Events
	Acalabrutinib
	Affected / at Risk (%)	# Events
Total	32/60 (53.3%)
Blood and lymphatic system disorders
Anaemia	1/60 (1.7%)	1
Cardiac disorders
Atrial fibrillation	1/60 (1.7%)	1
Cardiac failure congestive	2/60 (3.3%)	2
Ventricular fibrillation	1/60 (1.7%)	1
Gastrointestinal disorders
Diarrhoea	1/60 (1.7%)	1
Inguinal hernia	1/60 (1.7%)	1
General disorders
Gait disturbance	1/60 (1.7%)	1
Influenza like illness	1/60 (1.7%)	1
Injection site haemorrhage	1/60 (1.7%)	1
Non-cardiac chest pain	2/60 (3.3%)	4
Pyrexia	1/60 (1.7%)	1
Infections and infestations
Bronchopulmonary aspergillosis	2/60 (3.3%)	2
Cellulitis	1/60 (1.7%)	1
Clostridium difficile colitis	1/60 (1.7%)	1
Diverticulitis	1/60 (1.7%)	1
Lower respiratory tract infection	1/60 (1.7%)	1
Pneumonia	7/60 (11.7%)	8
Pneumonia mycoplasmal	1/60 (1.7%)	1
Pneumonia respiratory syncytial viral	1/60 (1.7%)	1
Pneumonia viral	1/60 (1.7%)	1
Pulmonary sepsis	1/60 (1.7%)	1
Respiratory tract infection	1/60 (1.7%)	1
Sepsis	3/60 (5%)	3
Injury, poisoning and procedural complications
Hip fracture	1/60 (1.7%)	1
Respiratory fume inhalation disorder	1/60 (1.7%)	1
Spinal fracture	1/60 (1.7%)	1
Splenic rupture	1/60 (1.7%)	1
Investigations
Transaminases increased	1/60 (1.7%)	1
Metabolism and nutrition disorders
Hyponatraemia	1/60 (1.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/60 (1.7%)	1
Lumbar spinal stenosis	1/60 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/60 (1.7%)	1
Chronic myelomonocytic leukaemia	1/60 (1.7%)	1
Gastrointestinal adenocarcinoma	1/60 (1.7%)	1
Malignant melanoma in situ	1/60 (1.7%)	1
Squamous cell carcinoma	1/60 (1.7%)	1
Nervous system disorders
Cerebrovascular accident	1/60 (1.7%)	1
Dizziness	1/60 (1.7%)	1
Dysarthria	1/60 (1.7%)	1
Encephalopathy	1/60 (1.7%)	1
Syncope	3/60 (5%)	3
Psychiatric disorders
Confusional state	1/60 (1.7%)	2
Renal and urinary disorders
Haematuria	1/60 (1.7%)	1
Renal tubular necrosis	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/60 (1.7%)	2
Dyspnoea	2/60 (3.3%)	2
Vascular disorders
Hypertension	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Acalabrutinib
	Affected / at Risk (%)	# Events
Total	60/60 (100%)
Blood and lymphatic system disorders
Anaemia	10/60 (16.7%)	25
Eosinophilia	1/60 (1.7%)	2
Increased tendency to bruise	1/60 (1.7%)	1
Iron deficiency anaemia	1/60 (1.7%)	1
Leukocytosis	2/60 (3.3%)	2
Lymph node pain	2/60 (3.3%)	3
Lymphocytosis	4/60 (6.7%)	5
Neutropenia	9/60 (15%)	18
Pancytopenia	1/60 (1.7%)	1
Polycythaemia	1/60 (1.7%)	2
Spontaneous haemorrhage	1/60 (1.7%)	1
Thrombocytopenia	4/60 (6.7%)	7
Cardiac disorders
Arrhythmia	1/60 (1.7%)	1
Atrial fibrillation	1/60 (1.7%)	1
Atrial flutter	1/60 (1.7%)	1
Cardiac arrest	1/60 (1.7%)	1
Cardiac failure congestive	2/60 (3.3%)	2
Cardiomyopathy	1/60 (1.7%)	1
Cardiorenal syndrome	1/60 (1.7%)	1
Extrasystoles	1/60 (1.7%)	1
Left ventricular dysfunction	1/60 (1.7%)	1
Mitral valve incompetence	1/60 (1.7%)	1
Palpitations	2/60 (3.3%)	2
Sinus bradycardia	2/60 (3.3%)	3
Sinus tachycardia	1/60 (1.7%)	1
Tachycardia	1/60 (1.7%)	1
Ventricular arrhythmia	1/60 (1.7%)	1
Ear and labyrinth disorders
Ear discomfort	2/60 (3.3%)	2
Ear pain	2/60 (3.3%)	2
Hypoacusis	1/60 (1.7%)	1
Middle ear effusion	1/60 (1.7%)	1
Tinnitus	4/60 (6.7%)	4
Vertigo	3/60 (5%)	3
Endocrine disorders
Goitre	1/60 (1.7%)	1
Hyperparathyroidism	1/60 (1.7%)	1
Thyroid mass	1/60 (1.7%)	1
Eye disorders
Cataract	2/60 (3.3%)	2
Conjunctival haemorrhage	1/60 (1.7%)	1
Dry eye	1/60 (1.7%)	1
Ocular hyperaemia	1/60 (1.7%)	1
Retinal tear	1/60 (1.7%)	1
Retinopathy	1/60 (1.7%)	1
Vision blurred	1/60 (1.7%)	1
Vitreous floaters	2/60 (3.3%)	2
Vitreous haemorrhage	1/60 (1.7%)	1
Gastrointestinal disorders
Abdominal discomfort	4/60 (6.7%)	4
Abdominal distension	3/60 (5%)	3
Abdominal pain	7/60 (11.7%)	8
Abdominal pain lower	1/60 (1.7%)	1
Ascites	1/60 (1.7%)	1
Barrett's oesophagus	1/60 (1.7%)	1
Cheilitis	1/60 (1.7%)	1
Colitis	1/60 (1.7%)	1
Constipation	10/60 (16.7%)	12
Dental caries	1/60 (1.7%)	1
Diarrhoea	32/60 (53.3%)	50
Dry mouth	5/60 (8.3%)	5
Dyspepsia	1/60 (1.7%)	1
Dysphagia	1/60 (1.7%)	1
Enterocolitis	1/60 (1.7%)	1
Gastric polyps	1/60 (1.7%)	1
Gastritis	1/60 (1.7%)	1
Gastrointestinal haemorrhage	1/60 (1.7%)	1
Gastrooesophageal reflux disease	4/60 (6.7%)	4
Haematochezia	1/60 (1.7%)	1
Haemorrhoids	2/60 (3.3%)	2
Hiatus hernia	2/60 (3.3%)	2
Large intestine polyp	4/60 (6.7%)	4
Nausea	15/60 (25%)	16
Oesophagitis	1/60 (1.7%)	1
Oral blood blister	1/60 (1.7%)	2
Oral pain	1/60 (1.7%)	2
Stomatitis	4/60 (6.7%)	6
Toothache	2/60 (3.3%)	2
Umbilical hernia	1/60 (1.7%)	1
Varices oesophageal	1/60 (1.7%)	1
Vomiting	6/60 (10%)	7
General disorders
Asthenia	2/60 (3.3%)	2
Chest pain	2/60 (3.3%)	2
Chills	6/60 (10%)	6
Cyst	1/60 (1.7%)	1
Fatigue	15/60 (25%)	21
Feeling cold	1/60 (1.7%)	1
Gait disturbance	1/60 (1.7%)	1
Hypothermia	1/60 (1.7%)	1
Inflammation	1/60 (1.7%)	1
Influenza like illness	7/60 (11.7%)	7
Localised oedema	5/60 (8.3%)	7
Malaise	3/60 (5%)	3
Non-cardiac chest pain	5/60 (8.3%)	6
Oedema	3/60 (5%)	3
Oedema peripheral	10/60 (16.7%)	12
Pain	3/60 (5%)	3
Peripheral swelling	3/60 (5%)	3
Pyrexia	12/60 (20%)	17
Hepatobiliary disorders
Cholangitis	1/60 (1.7%)	1
Cholelithiasis	1/60 (1.7%)	1
Portal hypertension	1/60 (1.7%)	1
Immune system disorders
Drug hypersensitivity	1/60 (1.7%)	1
Hypersensitivity	2/60 (3.3%)	2
Hypogammaglobulinaemia	2/60 (3.3%)	2
Immunodeficiency	1/60 (1.7%)	1
Infections and infestations
Bronchiolitis	1/60 (1.7%)	1
Bronchitis	4/60 (6.7%)	4
Cellulitis	1/60 (1.7%)	1
Chronic sinusitis	1/60 (1.7%)	1
Clostridium difficile colitis	1/60 (1.7%)	1
Clostridium difficile infection	3/60 (5%)	5
Conjunctivitis	2/60 (3.3%)	2
Diverticulitis	1/60 (1.7%)	1
Ear infection	1/60 (1.7%)	1
Enterocolitis infectious	1/60 (1.7%)	1
Escherichia bacteraemia	1/60 (1.7%)	1
Folliculitis	2/60 (3.3%)	2
Gastroenteritis	1/60 (1.7%)	1
Gingivitis	1/60 (1.7%)	1
Helicobacter infection	1/60 (1.7%)	1
Hepatitis b reactivation	1/60 (1.7%)	1
Herpes zoster	2/60 (3.3%)	2
Hordeolum	1/60 (1.7%)	1
Infected bite	1/60 (1.7%)	1
Influenza	2/60 (3.3%)	2
Kidney infection	1/60 (1.7%)	1
Localised infection	1/60 (1.7%)	2
Lower respiratory tract infection	2/60 (3.3%)	8
Nail infection	1/60 (1.7%)	1
Nasopharyngitis	1/60 (1.7%)	1
Onychomycosis	1/60 (1.7%)	1
Oral fungal infection	1/60 (1.7%)	1
Oral herpes	2/60 (3.3%)	3
Otitis media	3/60 (5%)	6
Pneumonia	8/60 (13.3%)	13
Pseudomonas infection	1/60 (1.7%)	1
Pyelitis	1/60 (1.7%)	1
Pyelonephritis	1/60 (1.7%)	1
Pyuria	1/60 (1.7%)	1
Respiratory tract infection	1/60 (1.7%)	5
Rhinitis	1/60 (1.7%)	1
Rhinovirus infection	1/60 (1.7%)	1
Sinusitis	9/60 (15%)	16
Skin infection	3/60 (5%)	3
Strongyloidiasis	1/60 (1.7%)	1
Tinea infection	1/60 (1.7%)	1
Tooth infection	2/60 (3.3%)	2
Upper respiratory tract infection	20/60 (33.3%)	34
Urinary tract infection	8/60 (13.3%)	17
Vulvovaginal mycotic infection	2/60 (3.3%)	5
Injury, poisoning and procedural complications
Ankle fracture	1/60 (1.7%)	3
Aortic pseudoaneurysm	1/60 (1.7%)	1
Arthropod bite	2/60 (3.3%)	2
Contusion	26/60 (43.3%)	32
Eye contusion	1/60 (1.7%)	1
Face injury	1/60 (1.7%)	1
Fall	9/60 (15%)	19
Ligament sprain	2/60 (3.3%)	3
Limb injury	1/60 (1.7%)	1
Lower limb fracture	1/60 (1.7%)	1
Mouth injury	1/60 (1.7%)	1
Patella fracture	1/60 (1.7%)	1
Post procedural haemorrhage	2/60 (3.3%)	2
Postoperative hypertension	1/60 (1.7%)	1
Procedural pain	1/60 (1.7%)	1
Rib fracture	2/60 (3.3%)	2
Road traffic accident	1/60 (1.7%)	1
Scratch	1/60 (1.7%)	1
Skin abrasion	1/60 (1.7%)	1
Skin laceration	3/60 (5%)	3
Spinal fracture	2/60 (3.3%)	3
Subdural haematoma	1/60 (1.7%)	1
Sunburn	1/60 (1.7%)	1
Thermal burn	1/60 (1.7%)	2
Transfusion reaction	1/60 (1.7%)	3
Wrist fracture	1/60 (1.7%)	1
Investigations
Alanine aminotransferase increased	3/60 (5%)	6
Anticonvulsant drug level increased	1/60 (1.7%)	1
Blood creatinine increased	2/60 (3.3%)	2
Blood phosphorus decreased	1/60 (1.7%)	1
Cardiac murmur	2/60 (3.3%)	2
Liver function test abnormal	1/60 (1.7%)	1
Liver function test increased	1/60 (1.7%)	1
Lymphocyte count decreased	1/60 (1.7%)	1
Lymphocyte count increased	6/60 (10%)	7
Neutrophil count decreased	7/60 (11.7%)	10
Platelet count decreased	6/60 (10%)	8
Prostatic specific antigen increased	1/60 (1.7%)	1
Transaminases increased	1/60 (1.7%)	1
Weight decreased	4/60 (6.7%)	7
Weight increased	8/60 (13.3%)	10
Metabolism and nutrition disorders
Decreased appetite	5/60 (8.3%)	8
Fluid overload	1/60 (1.7%)	1
Folate deficiency	1/60 (1.7%)	1
Hyperglycaemia	1/60 (1.7%)	1
Hyperkalaemia	4/60 (6.7%)	4
Hyperlipidaemia	1/60 (1.7%)	1
Hyperuricaemia	2/60 (3.3%)	2
Hypocalcaemia	1/60 (1.7%)	1
Hypoglycaemia	1/60 (1.7%)	1
Hypokalaemia	3/60 (5%)	6
Hypomagnesaemia	2/60 (3.3%)	2
Hyponatraemia	5/60 (8.3%)	13
Hypophosphataemia	2/60 (3.3%)	2
Hypovolaemia	1/60 (1.7%)	1
Increased appetite	1/60 (1.7%)	1
Iron deficiency	1/60 (1.7%)	1
Vitamin d deficiency	2/60 (3.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	14/60 (23.3%)	17
Arthritis	4/60 (6.7%)	5
Back pain	12/60 (20%)	18
Bone lesion	1/60 (1.7%)	1
Bone pain	2/60 (3.3%)	2
Diastasis recti abdominis	1/60 (1.7%)	1
Groin pain	1/60 (1.7%)	1
Intervertebral disc degeneration	1/60 (1.7%)	1
Joint range of motion decreased	1/60 (1.7%)	1
Joint swelling	1/60 (1.7%)	1
Muscle spasms	5/60 (8.3%)	7
Musculoskeletal chest pain	1/60 (1.7%)	1
Musculoskeletal pain	7/60 (11.7%)	8
Musculoskeletal stiffness	1/60 (1.7%)	1
Myalgia	5/60 (8.3%)	6
Neck pain	3/60 (5%)	3
Osteoarthritis	1/60 (1.7%)	1
Osteoporosis	1/60 (1.7%)	1
Osteosclerosis	1/60 (1.7%)	1
Pain in extremity	6/60 (10%)	9
Plantar fasciitis	1/60 (1.7%)	1
Scoliosis	1/60 (1.7%)	1
Spinal osteoarthritis	1/60 (1.7%)	1
Synovial cyst	1/60 (1.7%)	1
Tendon disorder	1/60 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acanthoma	1/60 (1.7%)	1
Basal cell carcinoma	5/60 (8.3%)	7
Dysplastic naevus	1/60 (1.7%)	1
Endometrial cancer	1/60 (1.7%)	1
Haemangioma of bone	1/60 (1.7%)	1
Haemangioma of skin	1/60 (1.7%)	1
Lentigo maligna	1/60 (1.7%)	1
Melanocytic naevus	1/60 (1.7%)	2
Seborrhoeic keratosis	1/60 (1.7%)	1
Skin papilloma	1/60 (1.7%)	1
Squamous cell carcinoma of lung	1/60 (1.7%)	1
Squamous cell carcinoma of skin	5/60 (8.3%)	10
Tumour flare	1/60 (1.7%)	1
Nervous system disorders
Arachnoid cyst	1/60 (1.7%)	1
Carpal tunnel syndrome	1/60 (1.7%)	1
Disturbance in attention	1/60 (1.7%)	1
Dizziness	19/60 (31.7%)	26
Headache	26/60 (43.3%)	29
Hypersomnia	1/60 (1.7%)	1
Hypoaesthesia	5/60 (8.3%)	5
Lethargy	2/60 (3.3%)	2
Memory impairment	2/60 (3.3%)	2
Migraine	1/60 (1.7%)	1
Migraine with aura	2/60 (3.3%)	2
Neuralgia	1/60 (1.7%)	1
Neuropathy peripheral	1/60 (1.7%)	1
Paraesthesia	3/60 (5%)	3
Peripheral sensory neuropathy	1/60 (1.7%)	1
Sciatica	1/60 (1.7%)	1
Sensory loss	1/60 (1.7%)	1
Sinus headache	1/60 (1.7%)	1
Syncope	2/60 (3.3%)	3
Tremor	4/60 (6.7%)	4
Psychiatric disorders
Adjustment disorder with depressed mood	1/60 (1.7%)	1
Anxiety	2/60 (3.3%)	2
Depression	7/60 (11.7%)	8
Insomnia	6/60 (10%)	6
Nightmare	1/60 (1.7%)	1
Sleep disorder	1/60 (1.7%)	1
Renal and urinary disorders
Acute kidney injury	1/60 (1.7%)	2
Chronic kidney disease	1/60 (1.7%)	2
Dysuria	2/60 (3.3%)	3
Glomerulosclerosis	1/60 (1.7%)	1
Haematuria	8/60 (13.3%)	9
Micturition urgency	2/60 (3.3%)	2
Nephrolithiasis	2/60 (3.3%)	2
Nocturia	4/60 (6.7%)	6
Pollakiuria	5/60 (8.3%)	5
Renal impairment	1/60 (1.7%)	1
Stress urinary incontinence	1/60 (1.7%)	1
Urinary incontinence	1/60 (1.7%)	1
Urinary retention	3/60 (5%)	3
Reproductive system and breast disorders
Adnexa uteri cyst	1/60 (1.7%)	1
Prostatic obstruction	1/60 (1.7%)	1
Spermatocele	1/60 (1.7%)	1
Vaginal haemorrhage	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Apnoea	1/60 (1.7%)	1
Asthma	1/60 (1.7%)	3
Bronchiectasis	1/60 (1.7%)	1
Bronchitis chronic	1/60 (1.7%)	1
Cough	19/60 (31.7%)	25
Dyspnoea	11/60 (18.3%)	11
Dyspnoea exertional	2/60 (3.3%)	3
Epistaxis	4/60 (6.7%)	6
Haemoptysis	3/60 (5%)	4
Hiccups	1/60 (1.7%)	1
Laryngeal inflammation	1/60 (1.7%)	1
Nasal congestion	7/60 (11.7%)	8
Oropharyngeal pain	4/60 (6.7%)	5
Pleural effusion	3/60 (5%)	4
Pneumonia aspiration	1/60 (1.7%)	1
Productive cough	3/60 (5%)	3
Pulmonary mass	1/60 (1.7%)	1
Pulmonary oedema	1/60 (1.7%)	1
Respiratory failure	2/60 (3.3%)	2
Rhinitis allergic	4/60 (6.7%)	4
Rhinorrhoea	2/60 (3.3%)	2
Sinus congestion	1/60 (1.7%)	1
Sleep apnoea syndrome	2/60 (3.3%)	2
Sputum discoloured	1/60 (1.7%)	1
Upper-airway cough syndrome	9/60 (15%)	11
Wheezing	1/60 (1.7%)	1
Skin and subcutaneous tissue disorders
Acne	1/60 (1.7%)	1
Actinic keratosis	2/60 (3.3%)	2
Alopecia	2/60 (3.3%)	2
Blister	1/60 (1.7%)	1
Blood blister	1/60 (1.7%)	1
Cold sweat	1/60 (1.7%)	1
Dermal cyst	1/60 (1.7%)	1
Dermatitis acneiform	1/60 (1.7%)	1
Dry skin	4/60 (6.7%)	4
Ecchymosis	5/60 (8.3%)	5
Hyperhidrosis	6/60 (10%)	8
Hyperkeratosis	2/60 (3.3%)	2
Hypertrichosis	1/60 (1.7%)	1
Ingrown hair	1/60 (1.7%)	1
Night sweats	8/60 (13.3%)	11
Onychoclasis	2/60 (3.3%)	2
Petechiae	5/60 (8.3%)	6
Precancerous skin lesion	1/60 (1.7%)	1
Pruritus	6/60 (10%)	7
Purpura	3/60 (5%)	3
Rash	12/60 (20%)	13
Rash erythematous	1/60 (1.7%)	1
Rash maculo-papular	3/60 (5%)	5
Skin discolouration	1/60 (1.7%)	1
Skin exfoliation	1/60 (1.7%)	1
Skin haemorrhage	1/60 (1.7%)	1
Skin hyperpigmentation	1/60 (1.7%)	1
Skin lesion	7/60 (11.7%)	8
Skin mass	1/60 (1.7%)	1
Transient acantholytic dermatosis	1/60 (1.7%)	1
Vascular disorders
Aortic stenosis	1/60 (1.7%)	1
Deep vein thrombosis	2/60 (3.3%)	2
Haematoma	1/60 (1.7%)	1
Hot flush	1/60 (1.7%)	1
Hypertension	8/60 (13.3%)	10
Hypotension	5/60 (8.3%)	5
Intermittent claudication	1/60 (1.7%)	1
Lymphoedema	2/60 (3.3%)	3
Peripheral coldness	1/60 (1.7%)	1
Thrombophlebitis superficial	1/60 (1.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.