PXD101-CLN-6: A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas

• Sponsor: Onxeo (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00274651
• Collaborator: (none)
• Enrollment: 53
• Locations: 15
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Open-label, non-randomized trial to assess the effectiveness of PXD101 in patients with recurrent or refractory cutaneous or peripheral and other types of T-cell lymphomas. PXD101 is a new, potent histone deacetylase (HDAC) inhibitor. Patients are treated with belinostat(PXD101) 1000 mg/m2 on days 1-5 of a 21 day cycle.

Condition or Disease	Intervention/Treatment	Phase
Cutaneous T-Cell Lymphoma; Peripheral T-Cell Lymphoma; Non-Hodgkin's Lymphoma	Drug: belinostat	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A PXD101 1000 mg/m2 once daily for 5 days every 21 days	Drug: belinostat; Other Names: PXD101
Experimental: Arm B PXD101 1000 mg/m2 once daily for 5 days every 21 days	Drug: belinostat; Other Names: PXD101

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL) [throughout the study, or for a maximum of 2 years]

   Tumor response was assessed using Cheson (Cheson 2007) and SWAT criteria. The SWAT score represents the product of the percentage total body surface area (TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor.

2. Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL)) [throughout the study, or for a maximum of 2 years]

   Tumor response was assessed using the revised criteria of Cheson (Cheson 2007).Tumor assessments were done using conventional radiographic methods, e.g. CT or CT/PET.

Secondary Outcome Measures

1. Time to Progression [throughout the study, or for a maximum of 2 years]

   Time to progression was defined as the interval between the first date of treatment and the first notation of disease progression.

2. Time to Response [throughout the study, or for a maximum of 2 years]

   Time to response was defined as the interval between the first date of treatment and the first notation of response.

3. Duration of Response [throughout the study, or for a maximum of 2 years]

   Duration of response was defined as the time from first notation of response until the time of first notation of disease progression.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female with age > or = 18 years.

• Histologically confirmed diagnosis of cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL) or other T-cell non-Hodgkin's lymphoma (NHL).

• Must have failed at least one line of prior systemic therapy. No limitation in number of prior therapies. CTCL patients who are refractory or intolerant to oral Targretin are also eligible.

• The presence of measurable disease (defined as > or = 1 cm with radiographic imaging) for PTCL or stage 1B or greater disease for CTCL and assessable by the severity-weighted assessment tool (SWAT).

• Adequate bone marrow and hepatic function including the following:

• Absolute neutrophil count > or = 1,000 cells/mm3, platelets > or = 40,000/mm3

• Total bilirubin < or = 1.5 x upper normal limit or < or = 3 x upper normal limit if hepatic involvement

• AST (SGOT) (aspartate aminotransferase), ALT (SGPT) (alanine aminotransferase) < or = 2.5 x upper normal limit (< or = 5 x upper normal limit if hepatic involvement)

• Hemoglobin > or = 9.0 g/dL.

• Serum potassium within normal range.

• Karnofsky performance status > or = 70%.

• Estimated life expectancy > 3 months.

• Signed informed consent approved by the Institutional Review Board (IRB).

Exclusion Criteria:

• Anti-cancer therapies within 4 weeks of first PXD101 administration should be excluded unless toxicity from prior anti-cancer therapy has resolved or returned to baseline and cancer disease status warrants.

• Any use of investigational drugs within 4 weeks prior to study registration.

• Major surgery within 4 weeks of study drug administration.

• Prior allogeneic bone marrow transplant.

• A diagnosis of adult T-cell lymphoma/leukemia (ATLL) or precursor T-lymphoblastic lymphoma.

• Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures. However, patients with progressing CTCL whose open skin lesions are frequently infected may not be excluded from this trial at the discretion of Investigators.

• Clinically significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, and congestive heart failure related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, history of sustained ventricular tachycardia, history of ventricular fibrillation or Torsade de Pointes, bradycardia (HR<50bpm) with or without a pacemaker, bifascicular block with a right bundle branch block and a left anterior block, ischemic or severe valvular heart disease, a myocardial infarction within 6 months or a left ventricular ejection fraction < 40% (by echocardiogram [ECHO] or multigated acquisition scan [MUGA]) within 3 months of study enrolment.

• A marked baseline prolongation of QT/QTc ((corrected) QT) interval, e.g., repeated demonstration of a QTc interval > 450 milliseconds (msec). Long QT Syndrome; the required use of concomitant medication on belinostat infusion days that may cause Torsade de Pointes.

• Renal insufficiency defined as a calculated creatinine clearance of < 45 mL/min/1.73 m2.

• A history of allergic reactions attributed to compounds of similar chemical or biological composition to PXD101 and L-arginine.

• Clinically significant central nervous system disorders with altered mental status or psychiatric disorders precluding understanding of the informed consent process and/or completion of the necessary studies.

• Patients requiring treatment for other malignant diseases or less than 5 years post-treatment completion for an invasive malignant disease (excluding non-melanotic skin cancers or cervical cancer in-situ). Patients with any history of melanoma should be excluded.

• Pregnant or breast-feeding women, and women of childbearing age and potential, who are not willing to use effective contraception. Male patients and/or their fertile female partners who are not willing to use contraceptives during the trial.

• Known infection with HIV, human T-cell leukemia virus type-1 (HTLV-1), hepatitis B or hepatitis C.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leland Stanford Junior University	Stanford	California	United States	94305
2	Yale University School of Medicine	New Haven	Connecticut	United States	06520
3	Kansas City Cancer Center	Lenexa	Kansas	United States	66214
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	Boston University Medical Center	Boston	Massachusetts	United States	02118
6	NYU Medical Center	New York	New York	United States	10016
7	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
8	MD Anderson Cancer Center	Houston	Texas	United States	77030
9	Hopitaux du Haut Leveque	Pessac		France	33604
10	Hospital Purpan	Toulouse		France	31059
11	Universitatsklinikum Essen	Essen		Germany	45147
12	Hadassah University Hospital Ein Kerem	Jerusalem		Israel	91120
13	Rabin Medical Center	Petach Tikva		Israel	49100
14	Songklanagarind Hospital, Prince of Songkla University	Hat Yai		Thailand	90110
15	King Chulalongkorn Memorial Hospital	Patumwan		Thailand	10330

Sponsors and Collaborators

• Onxeo

Investigators

• Study Director: e-mail contact via [e-mail], Onxeo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Onxeo
• ClinicalTrials.gov Identifier: NCT00274651
• Other Study ID Numbers: PXD101-CLN-6
• First Posted: Jan 11, 2006
• Last Update Posted: Jul 28, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Onxeo: CTCL; PTCL; lymphoma; Non-Hodgkin's Lymphoma; Cutaneous T-Cell Lymphomas (CTCL); Peripheral T-Cell Lymphomas (PTCL); Other Types of Non-Hodgkin's Lymphoma; belinostat
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Belinostat

Study Results

Participant Flow

Arm/Group Title	Arm A (CTCL, ITT Population)	Arm B (PTCL, ITT Population)
Arm/Group Description	PXD101 1000 mg/m2 once daily for 5 days every 21 days	PXD101 1000 mg/m2 once daily for 5 days every 21 days
Period Title: Overall Study
STARTED	29	24
COMPLETED	1	4
NOT COMPLETED	28	20

Baseline Characteristics

Arm/Group Title	CTCL (ITT Population)	PTCL (ITT Population)	Total
Arm/Group Description	CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV	PTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV	Total of all reporting groups
Overall Participants	29	24	53
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (13.4)	58.8 (15.9)	61.7 (14.7)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 41.4%	12 50%	24 45.3%
>=65 years	17 58.6%	12 50%	29 54.7%
Sex: Female, Male (Count of Participants)
Female	15 51.7%	7 29.2%	22 41.5%
Male	14 48.3%	17 70.8%	31 58.5%
Region of Enrollment (participants) [Number]
United States	22 75.9%	17 70.8%	39 73.6%
France	2 6.9%	0 0%	2 3.8%
Israel	2 6.9%	1 4.2%	3 5.7%
Thailand	2 6.9%	6 25%	8 15.1%
Germany	1 3.4%	0 0%	1 1.9%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL)
Description	Tumor response was assessed using Cheson (Cheson 2007) and SWAT criteria. The SWAT score represents the product of the percentage total body surface area (TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor.
Time Frame	throughout the study, or for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

At termination OR was noted in 1/13 patients (Simon Stage 1). With 29 patients in the CTCL arm the demand for expansion to Simon Stage 2 lacked 5 patients and the study was stopped. Instead OR was done as secondary efficacy analysis (ITT and PP (per protocol)) with OR calculated without accounting for Simon design and with 95% confidence intervals

Arm/Group Title	Arm A (CTCL, ITT Population)
Arm/Group Description	CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV
Measure Participants	0

2. Primary Outcome

Title	Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL))
Description	Tumor response was assessed using the revised criteria of Cheson (Cheson 2007).Tumor assessments were done using conventional radiographic methods, e.g. CT or CT/PET.
Time Frame	throughout the study, or for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

Primary efficacy analysis is based on the ITT analysis set, where the OR are calculated, and the proportion ± 80% CI (confidence interval) specified by Koyama & Chen (2008) are presented

Arm/Group Title	PTCL (ITT Population)
Arm/Group Description	PTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV
Measure Participants	24
Number [percentage of patients with OR]	25

3. Secondary Outcome

Title	Time to Progression
Description	Time to progression was defined as the interval between the first date of treatment and the first notation of disease progression.
Time Frame	throughout the study, or for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

Time to Progression (ITT population) was estimated using the Kaplan-Meier method for CTCL and PTCL arms. As progression was not observed in six patients in Arm A and 10 patients in Arm B, a total of 37 patients progressed, and the the median time to progression and the full range (days) are presented.

Arm/Group Title	Arm A (CTCL, ITT Population)	Arm B (PTCL, ITT Population)
Arm/Group Description	CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV	PTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV
Measure Participants	23	14
Median (Full Range) [Days]	43	82

4. Secondary Outcome

Title	Time to Response
Description	Time to response was defined as the interval between the first date of treatment and the first notation of response.
Time Frame	throughout the study, or for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

Time to response (ITT population) was estimated using the Kaplan-Meier method for CTCL and PTCL arms. For 4 patients with CTCL and 6 patients with PTCL, response was recorded. The median time to response and the full range (days) are presented.

Arm/Group Title	Arm A (CTCL, ITT Population)	Arm B (PTCL, ITT Population)
Arm/Group Description	CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV	PTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV
Measure Participants	4	6
Median (Full Range) [Days]	40	100

5. Secondary Outcome

Title	Duration of Response
Description	Duration of response was defined as the time from first notation of response until the time of first notation of disease progression.
Time Frame	throughout the study, or for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

Duration of response (ITT population) was estimated by Kaplan-Meier method for CTCL/PTCL arms. 2 CTCL and 2 PTCL patients did not progress and were censored. Median duration of response and full range (days) are presented for 2 patients with CTCL and 4 patients with PTCL. The 2 CTCL patients being evaluable had response durations of 56 and 129 days

Arm/Group Title	Arm A (CTCL, ITT Population)	Arm B (PTCL, ITT Population)
Arm/Group Description	CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV	PTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV
Measure Participants	2	4
Median (Full Range) [Days]	83	109

6. Post-Hoc Outcome

Title	Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL)
Description	Tumor response was assessed using Cheson (Cheson 2007) and SWAT criteria. The SWAT score represents the product of the percentage total body surface area (TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor.
Time Frame	throughout the study, or for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

At termination OR was noted in 1/13 patients (Simon Stage 1). With 29 patients in the CTCL arm the demand for expansion to Simon Stage 2 lacked 5 patients and the study was stopped. Instead OR was done as secondary efficacy analysis (ITT and PP (per protocol)) with OR calculated without accounting for Simon design and with 95% confidence intervals

Arm/Group Title	Arm A (CTCL, ITT Population)
Arm/Group Description	CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV
Measure Participants	29
Number [participants]	4 13.8%

Adverse Events

Time Frame	Throughout study, up to 4 weeks after last drug administration
Adverse Event Reporting Description	Follow-up of the AE (adverse event) was required during the study and after completion, withdrawal or discontinuation of the study if the event was still ongoing. The Investigator was to continuously monitor patients with AEs until the event had returned to baseline or ≤ Grade 1 or until the patient started another type of antineoplastic therapy.
Arm/Group Title	Arm A (CTCL, ITT Population)		Arm B (PTCL, ITT Population)
Arm/Group Description	CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV		PTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV
All Cause Mortality
	Arm A (CTCL, ITT Population)		Arm B (PTCL, ITT Population)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A (CTCL, ITT Population)		Arm B (PTCL, ITT Population)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/29 (24.1%)		8/24 (33.3%)
Blood and lymphatic system disorders
Thrombocytopenia	0/29 (0%)	0	1/24 (4.2%)	1
Cardiac disorders
Ventricular fibrillation	0/29 (0%)	0	1/24 (4.2%)	1
Gastrointestinal disorders
Abdominal pain	1/29 (3.4%)	1	1/24 (4.2%)	3
Ileus paralytic	0/29 (0%)	0	1/24 (4.2%)	1
General disorders
Disease progression	1/29 (3.4%)	1	1/24 (4.2%)	1
Gait disturbance	1/29 (3.4%)	1	0/24 (0%)	0
Oedema peripheral	1/29 (3.4%)	1	0/24 (0%)	0
Pyrexia	0/29 (0%)	0	1/24 (4.2%)	1
Infections and infestations
Staphylococcal skin infection	1/29 (3.4%)	1	0/24 (0%)	0
Implant site abscess	1/29 (3.4%)	1	0/24 (0%)	0
Sepsis	2/29 (6.9%)	2	0/24 (0%)	0
Pneumonia	0/29 (0%)	0	1/24 (4.2%)	1
Catheter related infection	0/29 (0%)	0	1/24 (4.2%)	1
Upper respiratory tract infection	0/29 (0%)	0	1/24 (4.2%)	1
Metabolism and nutrition disorders
Dehydration	1/29 (3.4%)	1	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	0/29 (0%)	0	1/24 (4.2%)	1
Nervous system disorders
Apraxia	1/29 (3.4%)	1	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonitis	0/29 (0%)	0	1/24 (4.2%)	1
Vascular disorders
Jugular vein thrombosis	1/29 (3.4%)	1	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A (CTCL, ITT Population)		Arm B (PTCL, ITT Population)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/29 (100%)		23/24 (95.8%)
Blood and lymphatic system disorders
Eosinophilia	2/29 (6.9%)	3	1/24 (4.2%)	1
Lymphadenopathy	2/29 (6.9%)	3	1/24 (4.2%)	1
Thrombocytopenia	0/29 (0%)	0	3/24 (12.5%)	4
Anaemia	0/29 (0%)	0	2/24 (8.3%)	2
Cardiac disorders
Tachycardia	1/29 (3.4%)	2	3/24 (12.5%)	6
Ear and labyrinth disorders
Vertigo	2/29 (6.9%)	3	0/24 (0%)	0
Gastrointestinal disorders
Nausea	17/29 (58.6%)	29	16/24 (66.7%)	32
Constipation	5/29 (17.2%)	5	9/24 (37.5%)	10
Vomiting	8/29 (27.6%)	14	6/24 (25%)	19
Diarrhoea	4/29 (13.8%)	4	5/24 (20.8%)	10
Dyspepsia	3/29 (10.3%)	3	3/24 (12.5%)	4
Abdominal pain	3/29 (10.3%)	3	2/24 (8.3%)	4
Abdominal discomfort	0/29 (0%)	0	3/24 (12.5%)	4
Gastrooesophageal reflux disease	1/29 (3.4%)	1	2/24 (8.3%)	2
Abdominal distension	0/29 (0%)	0	2/24 (8.3%)	3
Stomatitis	0/29 (0%)	0	2/24 (8.3%)	2
General disorders
Fatigue	6/29 (20.7%)	11	8/24 (33.3%)	11
Pyrexia	5/29 (17.2%)	9	6/24 (25%)	16
Infusion site pain	6/29 (20.7%)	6	3/24 (12.5%)	3
Oedema peripheral	6/29 (20.7%)	7	1/24 (4.2%)	1
Injection site reaction	0/29 (0%)	0	5/24 (20.8%)	9
Asthenia	1/29 (3.4%)	1	2/24 (8.3%)	2
Chest pain	3/29 (10.3%)	3	0/24 (0%)	0
Chills	3/29 (10.3%)	3	0/24 (0%)	0
Disease progression	1/29 (3.4%)	1	2/24 (8.3%)	2
Gait disturbance	3/29 (10.3%)	3	0/24 (0%)	0
Oedema	1/29 (3.4%)	1	2/24 (8.3%)	2
Mucosal inflammation	2/29 (6.9%)	2	0/24 (0%)	0
Immune system disorders
Hypersensitivity	0/29 (0%)	0	2/24 (8.3%)	2
Infections and infestations
Upper respiratory tract infection	3/29 (10.3%)	3	2/24 (8.3%)	2
Cellulitis	2/29 (6.9%)	2	2/24 (8.3%)	2
Herpes simplex	2/29 (6.9%)	2	0/24 (0%)	0
Pneumonia	0/29 (0%)	0	2/24 (8.3%)	2
Sepsis	2/29 (6.9%)	2	0/24 (0%)	0
Skin infection	2/29 (6.9%)	2	0/24 (0%)	0
Tinea pedis	2/29 (6.9%)	2	0/24 (0%)	0
Investigations
Alanine aminotransferase increased	2/29 (6.9%)	2	2/24 (8.3%)	3
Aspartate aminotransferase increased	2/29 (6.9%)	2	2/24 (8.3%)	2
Blood alkaline phosphatase increased	1/29 (3.4%)	1	3/24 (12.5%)	3
Blood lactate dehydrogenase increased	3/29 (10.3%)	3	0/24 (0%)	0
Blood creatinine increased	2/29 (6.9%)	3	0/24 (0%)	0
Blood magnesium decreased	0/29 (0%)	0	2/24 (8.3%)	2
Blood uric acid increased	2/29 (6.9%)	2	0/24 (0%)	0
Body temperature increased	2/29 (6.9%)	2	0/24 (0%)	0
Metabolism and nutrition disorders
Anorexia	3/29 (10.3%)	3	5/24 (20.8%)	5
Hypokalaemia	3/29 (10.3%)	5	4/24 (16.7%)	9
Dehydration	1/29 (3.4%)	1	4/24 (16.7%)	4
Hypoalbuminaemia	1/29 (3.4%)	1	2/24 (8.3%)	2
Hypomagnesaemia	2/29 (6.9%)	2	0/24 (0%)	0
Decreased appetite	0/29 (0%)	0	2/24 (8.3%)	2
Musculoskeletal and connective tissue disorders
Pain in extremity	5/29 (17.2%)	6	5/24 (20.8%)	5
Myalgia	2/29 (6.9%)	3	3/24 (12.5%)	4
Muscular weakness	2/29 (6.9%)	2	2/24 (8.3%)	2
Back pain	2/29 (6.9%)	2	1/24 (4.2%)	1
Muscle spams	2/29 (6.9%)	3	1/24 (4.2%)	2
Neck pain	2/29 (6.9%)	2	0/24 (0%)	0
Nervous system disorders
Dizziness	6/29 (20.7%)	7	5/24 (20.8%)	8
Headache	6/29 (20.7%)	6	1/24 (4.2%)	1
Dysgeusia	3/29 (10.3%)	3	1/24 (4.2%)	1
Hypoparaesthesia	3/29 (10.3%)	3	0/24 (0%)	0
Psychiatric disorders
Confusional state	2/29 (6.9%)	2	2/24 (8.3%)	2
Insomnia	1/29 (3.4%)	1	2/24 (8.3%)	4
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/29 (13.8%)	4	2/24 (8.3%)	3
Cough	3/29 (10.3%)	3	2/24 (8.3%)	2
Hiccups	0/29 (0%)	0	2/24 (8.3%)	2
Nasal congestion	0/29 (0%)	0	2/24 (8.3%)	2
Skin and subcutaneous tissue disorders
Pruritus	7/29 (24.1%)	8	2/24 (8.3%)	2
Rash	4/29 (13.8%)	5	3/24 (12.5%)	3
Skin exfoliation	4/29 (13.8%)	4	0/24 (0%)	0
Rash maculo-papular	0/29 (0%)	0	2/24 (8.3%)	2
Vascular disorders
Flushing	1/29 (3.4%)	1	4/24 (16.7%)	4
Phlebitis	3/29 (10.3%)	3	1/24 (4.2%)	1
Hypotension	2/29 (6.9%)	2	0/24 (0%)	0

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.