Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01258998
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arm: 1
• Duration (Months): 56
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This phase II clinical trial studies how well Akt inhibitor MK2206 works in treating patients with relapsed lymphoma. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia	Drug: Akt inhibitor MK2206; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the objective response rate (ORR) of MK-2206 (Akt inhibitor MK2206) in patients with relapsed/refractory lymphoma.

SECONDARY OBJECTIVES:

1. Assess the progression free survival (PFS) of MK-2206 in patients with relapsed/refractory lymphoma.

2. Assess the safety and tolerability of MK-2206 monotherapy. III. Examine pretreatment phosphorylated v-akt murine thymoma viral oncogene homolog 1 (pAkt) protein expression by immunohistochemistry, and correlate the results with treatment response.

3. Examine the effect of therapy on serum cytokines and chemokines that regulate the tumor-promoting inflammatory process and/or immunity in patients with relapsed/refractory lymphoma, and correlate the results with treatment response.

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

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: Phase II Study of MK-2206 in Patients With Relapsed Lymphoma
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (Akt inhibitor MK2206) Patients receive Akt inhibitor MK2206 PO once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: Akt inhibitor MK2206; Given PO; Other Names: MK2206 ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [4 months]

   Complete Response (CR) Disappearance of all evidence of disease(a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative (b) Variably FDG-avid or PET negative; regression to normal size on CT Not palpable, nodules disappeared Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immuno histochemistry should be negative. Partial Response (PR) Regression of measurable disease and no new sites, 50% decrease in , sum of the product of the diameters SPD of up to 6 largest dominant masses; no increase in size of other nodes(a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT, 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen, Irrelevant if positive prior to therapy; cell type should be specified.

Secondary Outcome Measures

1. Progression-free Survival [From treatment start date until the date of first documented progression or date of death from any cause, whichever came first.]

   Kaplan-Meier method was used. The log-rank test was performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model was used to include multiple covariates in the time-to-event analysis.

2. Duration of Response [From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.]

   Kaplan-Meier method was used. The log-rank test was performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model was used to include multiple covariates in the time-to-event analysis.

3. Overall Survival [From the start of treatment to death or 30 days after removal from the study whichever occurs first]

   Number of surviving participants without disease progression or death for any reason at one year post treatment. Kaplan-Meier method was used.

4. Number of Participants With Change in Cytokine Levels With p Values <0.05 [Baseline to up to 30 days post-treatment]

   The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.

5. Number of Participants With Change in Chemokine Levels With p Values <0.05 [Baseline to up to 30 days post-treatment]

   The changes in the chemokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.

6. Number of Participants With Change in Biomarker Levels With p Values <0.05 [Baseline to up to 30 days post-treatment]

   The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.

7. Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days]

   Toxicity data will be summarized by frequency tables.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma may be included)

• Relapsed or refractory after at least one regimen and with no curative option with conventional therapy

• Bidimensionally measurable disease (at least 2 cm)

• No evidence of cerebral or meningeal involvement by lymphoma

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

• Signed informed consent form prior to enrollment

• Women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a women become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately

Exclusion Criteria:

• Burkitt's lymphoma, lymphoblastic lymphoma, chronic lymphocytic leukemia and cutaneous T-cell lymphoma

• Chemotherapy or radiation therapy or other investigational agents within 3 weeks prior to entering the study unless there is clear evidence of progression of disease and toxicity from previous treatment has resolved in which case study entry may be within 1 week of last treatment

• Previous radioimmunotherapy within 12 weeks

• Patients with known immunodeficiency virus (HIV) infection must not have cluster of differentiation (CD)4 cells < 400/mm^3 and who must not have a prior acquired immunodeficiency syndrome (AIDS)-defining diagnosis and cannot be on antiretroviral therapy for HIV

• Known active viral hepatitis

• Any serious active disease or co-morbid condition, which in the opinion of the principal investigator, will interfere with the safety or with compliance with the study

• Absolute neutrophil count < 1.5 x 10^9/L

• Platelets < 75 x 10^9/L

• Total bilirubin > 1.5 x upper limit of normal (ULN) (> 3 x ULN for patients with liver involvement)

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2.5 x ULN (> 5 x ULN for patients with liver involvement)

• Serum creatinine > 2 x ULN

• Hemoglobin (Hb)A1C > 8%

• Patients receiving any medications or substances that are inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP 450 3A4) are ineligible

• Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial

• Cardiovascular: baseline Fredericia corrected QT interval (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study

• Significant heart block or baseline bradycardia < 50 beats per minute (bpm) due to cardiac disease

• Patients who are pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Yasuhiro Oki, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01258998
• Other Study ID Numbers: NCI-2012-02890; NCI-2012-02890; NCI-2011-00275; 2010-0261; 8728; N01CM00039; P30CA016672; N01CM62202
• First Posted: Dec 13, 2010
• Last Update Posted: Nov 4, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Mycoses; Lymphoma; Leukemia; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Mycosis Fungoides; Sezary Syndrome; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Leukemia-Lymphoma, Adult T-Cell; Waldenstrom Macroglobulinemia; Lymphoma, Large-Cell, Anaplastic; Leukemia, Hairy Cell; Lymphomatoid Granulomatosis; Lymphoma, Extranodal NK-T-Cell; Intraocular Lymphoma; Leukemia, Large Granular Lymphocytic; Immunoblastic Lymphadenopathy; Recurrence

Study Results

Participant Flow

Recruitment Details	Recruitment Period: December 10, 2010 to February 20, 2013. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Period Title: Overall Study
STARTED	60
COMPLETED	59
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Akt Inhibitor MK2206)
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Overall Participants	60
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	21 35%
Male	39 65%
Region of Enrollment (participants) [Number]
United States	60 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	Complete Response (CR) Disappearance of all evidence of disease(a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative (b) Variably FDG-avid or PET negative; regression to normal size on CT Not palpable, nodules disappeared Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immuno histochemistry should be negative. Partial Response (PR) Regression of measurable disease and no new sites, 50% decrease in , sum of the product of the diameters SPD of up to 6 largest dominant masses; no increase in size of other nodes(a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT, 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen, Irrelevant if positive prior to therapy; cell type should be specified.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

Based on intent-to-treat analysis.

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	59
Complete Response (CR)	2 3.3%
Partial Response (PR)	6 10%

2. Secondary Outcome

Title	Progression-free Survival
Description	Kaplan-Meier method was used. The log-rank test was performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model was used to include multiple covariates in the time-to-event analysis.
Time Frame	From treatment start date until the date of first documented progression or date of death from any cause, whichever came first.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	59
Median (95% Confidence Interval) [months]	2.8

3. Secondary Outcome

Title	Duration of Response
Description	Kaplan-Meier method was used. The log-rank test was performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model was used to include multiple covariates in the time-to-event analysis.
Time Frame	From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	59
Median (Full Range) [months]	5.8

4. Secondary Outcome

Title	Overall Survival
Description	Number of surviving participants without disease progression or death for any reason at one year post treatment. Kaplan-Meier method was used.
Time Frame	From the start of treatment to death or 30 days after removal from the study whichever occurs first

Outcome Measure Data

Analysis Population Description

PI is not available, therefore, no data is available for reporting in this section due to the overall survival was not an outcome to be measured initially. All efforts were made to retrieve data.

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	0

5. Secondary Outcome

Title	Number of Participants With Change in Cytokine Levels With p Values <0.05
Description	The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Time Frame	Baseline to up to 30 days post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	36
Count of Participants [Participants]	36 60%

6. Secondary Outcome

Title	Number of Participants With Change in Chemokine Levels With p Values <0.05
Description	The changes in the chemokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Time Frame	Baseline to up to 30 days post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	36
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Number of Participants With Change in Biomarker Levels With p Values <0.05
Description	The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Time Frame	Baseline to up to 30 days post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	36
Count of Participants [Participants]	0 0%

8. Secondary Outcome

Title	Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description	Toxicity data will be summarized by frequency tables.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Akt Inhibitor MK2206
Arm/Group Description	Akt inhibitor MK2206 200 mg orally once a week, repeats every 28 days for up to 12 courses.
Measure Participants	59
Fatigue	12 20%
Anorexia	4 6.7%
Aspartate aminotransferase elevation	4 6.7%
Constipation	3 5%
Diarrhea	4 6.7%
Nausea	9 15%
Hyperglycemia	34 56.7%
Elevated creatinine	4 6.7%
Conjunctivitis	4 6.7%
Rash	31 51.7%
Dry skin	4 6.7%
Pruritus	6 10%
Anemia	5 8.3%
Thrombocytopenia	15 25%
Neutropenia	10 16.7%
Lymphopenia	13 21.7%

Adverse Events

Time Frame	Adverse Events (AEs) were collected from the time of the first treatment to discontinuation of participant in study, up to 3 years.
Arm/Group Title	Treatment (Akt Inhibitor MK2206)
Arm/Group Description	Akt inhibitor MK2206 orally once a week, repeats every 28 days for up to 12 courses.
All Cause Mortality
	Treatment (Akt Inhibitor MK2206)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Akt Inhibitor MK2206)
	Affected / at Risk (%)	# Events
Total	5/60 (8.3%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	1/60 (1.7%)	1
Neutrophil count decreased	1/60 (1.7%)	1
Lymphocyte count decreased	3/60 (5%)	3
Anemia	1/60 (1.7%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/60 (1.7%)	1
Hypercalcemia	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Akt Inhibitor MK2206)
	Affected / at Risk (%)	# Events
Total	59/60 (98.3%)
Blood and lymphatic system disorders
Alanine aminotransferase increased	1/60 (1.7%)	8
Alkaline phosphatase increased	1/60 (1.7%)	29
Anemia	11/60 (18.3%)	71
Aspartate aminotransferase increased	3/60 (5%)	12
Blood bilirubin increased	1/60 (1.7%)	6
Creatinine increased	1/60 (1.7%)	14
Edema limbs	1/60 (1.7%)	10
Edema trunk	1/60 (1.7%)	1
Hypercalcemia	1/60 (1.7%)	8
Hyperglycemia	5/60 (8.3%)	89
Hyperkalemia	2/60 (3.3%)	14
Hypernatremia	1/60 (1.7%)	4
Hypertriglyceridemia	1/60 (1.7%)	1
Hyperuricemia	1/60 (1.7%)	4
Hypoalbuminemia	3/60 (5%)	16
Hypocalcemia	1/60 (1.7%)	9
Hypoglycemia	2/60 (3.3%)	4
Hypokalemia	1/60 (1.7%)	6
Hypomagnesemia	1/60 (1.7%)	16
Hyponatremia	1/60 (1.7%)	5
Hypophosphatemia	1/60 (1.7%)	16
Leukocytosis	3/60 (5%)	13
Lymphedema	1/60 (1.7%)	2
Lymphocyte count decreased	1/60 (1.7%)	59
Neutrophil count decreased	3/60 (5%)	19
Platelet count decreased	3/60 (5%)	47
White blood cell decreased	3/60 (5%)	29
Cardiac disorders
Atrial fibrillation	1/60 (1.7%)	2
Chest pain - cardiac	1/60 (1.7%)	3
Hypertension	4/60 (6.7%)	8
Hypotension	1/60 (1.7%)	2
Left ventricular systolic dysfunction	1/60 (1.7%)	1
Non-cardiac chest pain	1/60 (1.7%)	1
Ear and labyrinth disorders
Ear pain	1/60 (1.7%)	1
Tinnitus	1/60 (1.7%)	5
Endocrine disorders
Hyperthyroidism	1/60 (1.7%)	1
Hypothyroidism	1/60 (1.7%)	5
Eye disorders
Blurred vision	1/60 (1.7%)	4
Conjunctivitis	1/60 (1.7%)	5
Dry eye	1/60 (1.7%)	2
Eye pain	1/60 (1.7%)	1
Gastrointestinal disorders
Abdominal pain	1/60 (1.7%)	4
Anorexia	1/60 (1.7%)	9
Colonic hemorrhage	1/60 (1.7%)	1
Constipation	1/60 (1.7%)	8
Dehydration	1/60 (1.7%)	2
Diarrhea	2/60 (3.3%)	12
Dry mouth	1/60 (1.7%)	1
Dyspepsia	1/60 (1.7%)	1
Dysphagia	2/60 (3.3%)	3
Gastroesophageal reflux disease	1/60 (1.7%)	1
Gastrointestinal disorders	3/60 (5%)	4
Mucositis oral	1/60 (1.7%)	1
Nausea	1/60 (1.7%)	15
Rectal hemorrhage	1/60 (1.7%)	1
Rectal pain	1/60 (1.7%)	1
Vomiting	1/60 (1.7%)	3
General disorders
Chills	1/60 (1.7%)	2
Fatigue	4/60 (6.7%)	24
Fever	1/60 (1.7%)	14
General disorders and administration site conditions	2/60 (3.3%)	4
Insomnia	1/60 (1.7%)	6
Lethargy	1/60 (1.7%)	2
Malaise	1/60 (1.7%)	3
Pain	2/60 (3.3%)	8
Weight loss	1/60 (1.7%)	1
Hepatobiliary disorders
Hepatobiliary disorders	1/60 (1.7%)	1
Pancreatitis	1/60 (1.7%)	1
Immune system disorders
Allergic rhinitis	2/60 (3.3%)	14
Infections and infestations
Infections and infestations	1/60 (1.7%)	4
Investigations
Investigations	1/60 (1.7%)	2
Musculoskeletal and connective tissue disorders
Arthritis	1/60 (1.7%)	3
Back pain	2/60 (3.3%)	2
Bone pain	2/60 (3.3%)	2
Flank pain	1/60 (1.7%)	1
Fracture	1/60 (1.7%)	1
Gait disturbance	1/60 (1.7%)	2
Musculoskeletal and connective tissue disorder	1/60 (1.7%)	2
Neck pain	1/60 (1.7%)	2
Pain in extremity	1/60 (1.7%)	1
Wrist fracture	1/60 (1.7%)	1
Nervous system disorders
Anxiety	2/60 (3.3%)	10
Confusion	1/60 (1.7%)	2
Depression	3/60 (5%)	8
Dizziness	1/60 (1.7%)	5
Facial nerve disorder	1/60 (1.7%)	1
Facial pain	1/60 (1.7%)	1
Headache	1/60 (1.7%)	10
Memory impairment	1/60 (1.7%)	1
Paresthesia	3/60 (5%)	5
Peripheral motor neuropathy	1/60 (1.7%)	1
Peripheral sensory neuropathy	1/60 (1.7%)	15
Seizure	1/60 (1.7%)	1
Tremor	1/60 (1.7%)	1
Psychiatric disorders
Psychiatric disorders	1/60 (1.7%)	1
Renal and urinary disorders
Renal and urinary disorders	1/60 (1.7%)	5
Urinary frequency	1/60 (1.7%)	2
Urinary retention	1/60 (1.7%)	1
Urinary tract infection	1/60 (1.7%)	1
Urinary tract pain	1/60 (1.7%)	1
Reproductive system and breast disorders
Erectile dysfunction	2/60 (3.3%)	2
Pelvic pain	1/60 (1.7%)	1
Vaginal discharge	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Chest wall pain	1/60 (1.7%)	4
Cough	1/60 (1.7%)	22
Dysarthria	1/60 (1.7%)	1
Dyspnea	1/60 (1.7%)	12
Epistaxis	1/60 (1.7%)	1
Mucosal infection	1/60 (1.7%)	1
Nasal congestion	1/60 (1.7%)	5
Pharyngitis	1/60 (1.7%)	1
Pharyngolaryngeal pain	1/60 (1.7%)	1
Pleural effusion	1/60 (1.7%)	1
Pneumonitis	1/60 (1.7%)	2
Postnasal drip	1/60 (1.7%)	1
Productive cough	1/60 (1.7%)	3
Sinus bradycardia	1/60 (1.7%)	1
Sinus tachycardia	1/60 (1.7%)	2
Sinusitis	1/60 (1.7%)	1
Sore throat	1/60 (1.7%)	4
Upper respiratory infection	2/60 (3.3%)	11
Wheezing	1/60 (1.7%)	1
Skin and subcutaneous tissue disorders
Bruising	1/60 (1.7%)	1
Bullous dermatitis	1/60 (1.7%)	1
Dry skin	1/60 (1.7%)	7
Flushing	1/60 (1.7%)	1
Pruritus	1/60 (1.7%)	16
Rash acneiform	1/60 (1.7%)	1
Rash maculo-papular	2/60 (3.3%)	59
Skin and subcutaneous tissue disorders	1/60 (1.7%)	4
Skin hypopigmentation	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.