MLN9708 (Ixazomib) in Combination With Panobinostat and Dexamethasone in Multiple Myeloma

• Sponsor: Jason Valent (Other)
• Overall Status: Completed
• CT.gov ID: NCT02057640
• Collaborator: (none)
• Enrollment: 16
• Locations: 2
• Arm: 1
• Actual Duration (Months): 47.8
• Patients Per Site: 8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will look at the safety and tolerability of the new drug MLN9708 in combination with the existing drugs panobinostat and dexamethasone among patients with relapsed or refractory multiple myeloma. This study will also look at the response and clinical benefit of the treatment and the progression-free survival and overall survival of study participants.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Kahler Disease; Plasma-Cell Myeloma; Myelomatosis	Drug: Panobinostat; Drug: Dexamethasone; Drug: MLN9708	Phase 1/Phase 2

Detailed Description

The primary objective of this study is to define the tolerability and safety of MLN9708 (ixazomib) administered on a day 1,8,15 every 28 day schedule up to 4mg in combination with fixed doses of panobinostat and dexamethasone in patients with relapsed or refractory myeloma.

The secondary objectives of this study are to assess response and clinical benefit response rates according to international uniform response criteria and adapted EBMT criteria, respectively. And to assess progression-free survival (PFS) and overall survival (OS).

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of MLN9708 (Ixazomib) in Combination With Panobinostat and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
• Actual Study Start Date: May 22, 2014
• Actual Primary Completion Date: May 15, 2018
• Actual Study Completion Date: May 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination therapy: Panobinostat, dexamethasone, MLN9708 Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 4mg on day 1, 8, 15, 28	Drug: Panobinostat; 20mg, on day 1, 3, 5, 15, 17, 19, 28; Drug: Dexamethasone; 20mg, on day 1, 2, 8, 9, 15, 16, 28; Drug: MLN9708; 4mg on day 1, 8, 15, 28; Other Names: Ixazomib

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicity According to CTCAE Version 4.03 [at 28 days from start of treatment]

   Number of Participants with Dose Limiting Toxicity of MLN9708 (lxazomib) according to CTCAE version 4.03

Secondary Outcome Measures

1. Response to Combination Therapy (Panobinostat, Dexamethasone, MLN9708) [4 months (102 days)]

   Response to intervention as measured by international uniform response criteria and clinical benefit response according to modified EBMT response criteria, comparing myeloma panels obtained at the beginning of each cycle that include SPEP, 24 h UPEP, serum and urine IFEs, and serum free light chains to results at screening. In addition a baseline bone marrow exam and skeletal survey will be obtained and repeated as clinically indicated and for assessment of complete remission (bone marrow)

2. Progression-free Survival [1 year from start of treatment]

   Progression-free survival will be the number of days from study entry to progression or death of any cause, whichever comes first. Progression-free survival is survival with absence of progressive disease, defined by An increase of 25% from lowest response value in any one or more of the following: Serum M-component (absolute increase must be >0.5 g/100 ml) * Urine M-component (absolute increase must be >200mg per 24 h) Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >100 mg/l) Bone marrow plasma cell percentage (absolute % must be >10%) And / or: Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum calcium >11.5 mg/100 ml) that can be attributed solely to the plasma cell proliferative disorder

3. Overall Survival [up to 3 years from start of treatment]

   Overall survival for all will be the number of months from study entry to death from any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

• Patients must carry a diagnosis of symptomatic multiple myeloma according to international myeloma working group criteria and have relapsed or refractory disease according to international uniform response criteria and must have previously received therapy with a proteasome inhibitor and an IMiD™

• Must have measurable disease defined as any of the following: Serum m-spike ≥ 1g/dL, 24 h urine m-spike of at least 200mg/d, involved serum free light chains ≥ 100mg/L with abnormal serum free light chain ratio, bone marrow plasma cells of at least 30%

• ECOG PS ≤ 2

• No gastro-intestinal condition, that in the opinion of the treating physician or the principal investigator significantly limits oral absorption

• No serious uncontrolled coexisting medical condition

• Patients must meet the following laboratory criteria:

• ANC ≥ 1.0 x 10^9/L without use of pegfilgrastim in the preceding 21 days and without non-pegylated G-CSF or GM-CSF within 7 days prior to study entry

• Hemoglobin ≥ 8 g/dl (may be after transfusion of packed red blood cells or use of erythropoiesis stimulating agents)

• Platelets ≥ 70x 10^9/L without platelet transfusion 7 days prior to study entry

• AST and ALT ≤ 2.5 x ULN

• Serum bilirubin ≤ 1.5 x ULN

• Serum potassium ≥ LLN and serum magnesium ≥ LLN (electrolyte levels may be achieved with repletion or other supportive medications like potassium sparing diuretics)

• Creatinine clearance ≥ 30 mL/min according to Cockroft-Gault formula

• Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

• Baseline MUGA or ECHO must demonstrate LVEF ≥ 45%

• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to start of study treatment

• Male patients, even if surgically sterilized (i.e., status post vasectomy), have to either:

• Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study treatment, OR

• Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR

• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.

• Female patients have to fulfill one of the following:

• Be postmenopausal for at least 1 year before the Screening visit, OR

• Be surgically sterile, OR

• If of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study treatment

• Oral contraceptives are generally metabolized by CYP3A4. Since the induction potential of panobinostat to induce CYP3A4 is unknown, patients who are using oral contraceptives as a method of contraception, and are sexually active, should use another effective contraceptive method, AND Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR

• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

• At least 7 days must have passed since the last treatment with lenalidomide, pomalidomide, thalidomide, proteasome inhibitors, or low dose cyclophosphamide (up to 50mg daily), at least 21 days must have passed since the last treatment with daratumumab, elotuzumab, investigational therapy and most conventional chemotherapy including cyclophosphamide above 50mg per dose, bendamustine, doxorubicin, cisplatin, and etoposide; and at least 35 days since the last treatment with melphalan.

Exclusion Criteria:

• Prior anti-cancer treatment with MLN9708 (ixazomib), HDAC, DAC, HSP90 inhibitors or valproic acid

• Prior participation in a randomized controlled study that included MLN9708 (ixazomib) in one of the treatment arms independent of whether assigned to MLN9708 (ixazomib) or not

• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.

• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:

• History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible)

• Any history of ventricular fibrillation or torsade de pointes

• Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.

• Screening ECG with a QTcF > 470 msec (QTcF=QT/3√RR). If potassium or magnesium blood levels are below normal limits, consider repeating ECG after correction of these electrolytes

• Right bundle branch block + left anterior hemiblock (bifascicular block)

• Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug

• Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)

• Impairment of GI function or GI disease that may significantly alter the swallowing absorption of panobinostat and MLN9708

• Patients with diarrhea > CTCAE (version 4.03) grade 2

• Patient has ≥ Grade 3 peripheral neuropathy, or ≥ Grade 2 with pain on clinical examination during the screening period.

• Patients with known metastasis of malignant plasma cells to the central nervous system (if not suspected nonspecific testing is required)

• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol

• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug. If an alternative medication that does not risk QT prolongation can safely be used in the opinion of the treating physician and the treatment is changed to that medication, the patient may be enrolled.

• Patients who have not passed the nadir of bone marrow suppression from previous anti-myeloma therapy yet. If in doubt, serial CBCs with differential should be obtained.

• The corticosteroids prednisone and dexamethasone may be continued until the day before treatment start if all related adverse events are controlled at CTCAE version 4.03 grade ≤ 1.

• Patients who have received radiation therapy to more than half of the pelvis or more than half of the spine within ≤ 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.

• Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy

• Systemic treatment, within 14 days before study enrollment, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.

• Ongoing or active systemic infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus hepatitis.

• Concurrent diagnosis of another malignancy if either systemic treatment or surgery is expected to be required within 2 years from study entry.

• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

• Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff.

• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment unless the patient is felt to have fully recovered and any antibiotics that are continued are either beta lactam antibiotics or are specifically allowed on study.

• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
2	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Jason Valent

Investigators

• Principal Investigator: Jason Valent, MD, Case Comprehensive Cancer Center
• Principal Investigator: Ehsan Malek, MD, Case Comprehensive Cancer Center

Study Documents (Full-Text)

• Informed Consent Form - Apr 20, 2017
• Study Protocol and Statistical Analysis Plan - Apr 3, 2017

More Information

Publications

None provided.

• Responsible Party: Jason Valent, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02057640
• Other Study ID Numbers: CASE4A13
• First Posted: Feb 7, 2014
• Last Update Posted: Dec 11, 2019
• Last Verified: Dec 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Ixazomib; Panobinostat

Study Results

Participant Flow

Arm/Group Title	DL1 - 3mg Lxazomib	DL2 - 4mg Lxazomib
Arm/Group Description	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
Period Title: Weeks 1-4
STARTED	4	3
COMPLETED	4	3
NOT COMPLETED	0	0
Period Title: Weeks 1-4
STARTED	0	9
COMPLETED	0	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Phase I	Phase I/II	Total
Arm/Group Description	Ixazomib - DL 1	Ixazomib -DL2	Total of all reporting groups
Overall Participants	4	12	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 75%	5 41.7%	8 50%
>=65 years	1 25%	7 58.3%	8 50%
Sex: Female, Male (Count of Participants)
Female	2 50%	4 33.3%	6 37.5%
Male	2 50%	8 66.7%	10 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 8.3%	1 6.3%
Not Hispanic or Latino	4 100%	11 91.7%	15 93.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	4 100%	11 91.7%	15 93.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 8.3%	1 6.3%
Region of Enrollment (Count of Participants)
United States	4 100%	12 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicity According to CTCAE Version 4.03
Description	Number of Participants with Dose Limiting Toxicity of MLN9708 (lxazomib) according to CTCAE version 4.03
Time Frame	at 28 days from start of treatment

Outcome Measure Data

Analysis Population Description

All participants who received treatment in the phase I portion of the study

Arm/Group Title	Dose Levels 1
Arm/Group Description	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
Measure Participants	4
Count of Participants [Participants]	4 100%

2. Secondary Outcome

Title	Response to Combination Therapy (Panobinostat, Dexamethasone, MLN9708)
Description	Response to intervention as measured by international uniform response criteria and clinical benefit response according to modified EBMT response criteria, comparing myeloma panels obtained at the beginning of each cycle that include SPEP, 24 h UPEP, serum and urine IFEs, and serum free light chains to results at screening. In addition a baseline bone marrow exam and skeletal survey will be obtained and repeated as clinically indicated and for assessment of complete remission (bone marrow)
Time Frame	4 months (102 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DL1 - 3mg Lxazomib	DL2 - 4mg Lxazomib
Arm/Group Description	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
Measure Participants	4	12
Number [participants]	0 0%	0 0%

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival will be the number of days from study entry to progression or death of any cause, whichever comes first. Progression-free survival is survival with absence of progressive disease, defined by An increase of 25% from lowest response value in any one or more of the following: Serum M-component (absolute increase must be >0.5 g/100 ml) * Urine M-component (absolute increase must be >200mg per 24 h) Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >100 mg/l) Bone marrow plasma cell percentage (absolute % must be >10%) And / or: Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum calcium >11.5 mg/100 ml) that can be attributed solely to the plasma cell proliferative disorder
Time Frame	1 year from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DL1 - 3mg Lxazomib	DL2 - 4mg Lxazomib
Arm/Group Description	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
Measure Participants	4	12
Median (95% Confidence Interval) [months]	1.2	3.5

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival for all will be the number of months from study entry to death from any cause.
Time Frame	up to 3 years from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DL1 - 3mg Lxazomib	DL2 - 4mg Lxazomib
Arm/Group Description	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28
Measure Participants	4	12
Median (95% Confidence Interval) [months]	12.8	17.6

Adverse Events

Time Frame	30 days post last study drug administration
Arm/Group Title	DL1 - 3mg Lxazomib		DL2 - 4mg Lxazomib
Arm/Group Description	Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 3mg on day 1, 8, 15, 28		Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 4mg on day 1, 8, 15, 28
All Cause Mortality
	DL1 - 3mg Lxazomib		DL2 - 4mg Lxazomib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		9/12 (75%)
Serious Adverse Events
	DL1 - 3mg Lxazomib		DL2 - 4mg Lxazomib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		5/12 (41.7%)
Cardiac disorders
Atrial Fibrillation	0/4 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Gastric hemorrhage	0/4 (0%)		1/12 (8.3%)
Infections and infestations
Hyperviscosity	1/4 (25%)		0/12 (0%)
Lung Infection	0/4 (0%)		2/12 (16.7%)
Renal and urinary disorders
Urinary retention	1/4 (25%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Skin Infection	0/4 (0%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	DL1 - 3mg Lxazomib		DL2 - 4mg Lxazomib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		12/12 (100%)
Blood and lymphatic system disorders
anemia	1/4 (25%)		4/12 (33.3%)
Lymphocyte count decreased	0/4 (0%)		4/12 (33.3%)
Lymphocyte count increased	0/4 (0%)		1/12 (8.3%)
Neutrophil count decreased	0/4 (0%)		3/12 (25%)
Platelet count decreased	1/4 (25%)		4/12 (33.3%)
White blood cell decreased	0/4 (0%)		3/12 (25%)
Eye disorders
blurred vision	0/4 (0%)		1/12 (8.3%)
Gastrointestinal disorders
constipation	0/4 (0%)		2/12 (16.7%)
abdominal pain	0/4 (0%)		2/12 (16.7%)
dyspepsia	0/4 (0%)		1/12 (8.3%)
flatulence	1/4 (25%)		0/12 (0%)
vomiting	0/4 (0%)		3/12 (25%)
Diarrhea	1/4 (25%)		5/12 (41.7%)
Nausea	3/4 (75%)		6/12 (50%)
Taste changes	0/4 (0%)		1/12 (8.3%)
Belching	0/4 (0%)		1/12 (8.3%)
General disorders
fever	0/4 (0%)		2/12 (16.7%)
edema face	0/4 (0%)		1/12 (8.3%)
fatigue	0/4 (0%)		3/12 (25%)
irritability	0/4 (0%)		2/12 (16.7%)
Edema Limbs	1/4 (25%)		1/12 (8.3%)
Pain	0/4 (0%)		1/12 (8.3%)
Infections and infestations
respiratory infection	1/4 (25%)		0/12 (0%)
Breast infection	0/4 (0%)		1/12 (8.3%)
Bronchial infection	0/4 (0%)		1/12 (8.3%)
Shingles	0/4 (0%)		1/12 (8.3%)
Investigations
creatinine increased	0/4 (0%)		2/12 (16.7%)
Metabolism and nutrition disorders
anorexia	0/4 (0%)		2/12 (16.7%)
Hypokalemia	1/4 (25%)		2/12 (16.7%)
Hyperglycemia	0/4 (0%)		1/12 (8.3%)
Hypalbuminemia	0/4 (0%)		1/12 (8.3%)
Hypocalcemia	0/4 (0%)		1/12 (8.3%)
Hypomagnesemia	0/4 (0%)		1/12 (8.3%)
Hypohosphatemia	0/4 (0%)		2/12 (16.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)		0/12 (0%)
Muscle weakness lower limb	0/4 (0%)		1/12 (8.3%)
Nervous system disorders
dizziness	0/4 (0%)		2/12 (16.7%)
headache	1/4 (25%)		2/12 (16.7%)
tremors	0/4 (0%)		2/12 (16.7%)
Dysgeusia	0/4 (0%)		1/12 (8.3%)
Cognitive disturbance	1/4 (25%)		0/12 (0%)
Psychiatric disorders
Depression	0/4 (0%)		1/12 (8.3%)
Insomnia	0/4 (0%)		4/12 (33.3%)
Renal and urinary disorders
Hemoglobinuria	0/4 (0%)		2/12 (16.7%)
Respiratory, thoracic and mediastinal disorders
Postnasal drip	0/4 (0%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
scalp psoriasis	1/4 (25%)		0/12 (0%)
bruising	0/4 (0%)		1/12 (8.3%)
Pruritus	0/4 (0%)		1/12 (8.3%)
Rash maculo-papular	0/4 (0%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.