Phase 2 Study of Oral IXAZOMIB in Adult Participants With Relapsed and/or Refractory Follicular Lymphoma

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01939899
• Collaborator: (none)
• Enrollment: 29
• Locations: 14
• Arm: 1
• Actual Duration (Months): 40.7
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the anti-tumor activity of oral Ixazomib as measured by overall response rate (ORR) in adult participants with relapsed and/or refractory follicular lymphoma (FL).

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Drug: IXAZOMIB	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter, Phase 2 Study of Oral IXAZOMIB (MLN9708) in Adult Patients With Relapsed and/or Refractory Follicular Lymphoma
• Actual Study Start Date: Oct 31, 2013
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Mar 23, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: IXAZOMIB Ixazomib 4, 5.3 and 7 milligram (mg), orally, once on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days, for up to Cycle 29 or until disease progression or unacceptable toxicity at lead-in phase for participants with NHL. After completion of lead-in phase, participants will continue into Phase 2. Participants in Phase 2 will receive Ixazomib at RP2D dose, orally, once weekly on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days , for up to Cycle 29 or until disease progression or unacceptable toxicity in Phase 2 for participants with RRFL.

Drug: IXAZOMIB; Each 28-day treatment cycle will include oral administration of IXAZOMIB on Days 1, 8, and 15 followed by a rest period of 13 days.; Other Names: MLN9708

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Overall Response Rate (ORR) [Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies]

   ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using the international Working Group criteria for participants CR: disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.

Secondary Outcome Measures

1. Lead-in Dose Finding Phase: Recommended Phase 2 Dose (RP2D) [Baseline up to Cycle 1 Day 28]

2. Progression Free Survival (PFS) [Time from the date of first dose of study treatment to the date of first documented PD or death (approximately up to Day 802)]

   PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death. Participants without documentation of PD will be censored at the date of last response assessment that is SD or better. Participants without response assessment will be censored at the date of first dose.

3. Phase 2: Rate of Disease Control [Baseline or until occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 805)]

   Rate of disease control is defined as percentage of participants who achieved a SD or better for greater than or equal to (>=) 6 months.

4. Time to Response (TTR) [Time from the date of first dose of study treatment to the date of first documented PR or better response or death (approximately up to Day 802)]

   TTR is defined as the time from the date of first dose of study treatment to the date of the first documentation of a PR or better response in a participant who responded.

5. Duration of Response (DOR) [Time from the date of first documentation of a response to the date of first documented PD (approximately up to Day 802)]

   The DOR is defined as the time from the date of first documentation of a response to the date of first documented PD. Responders without documentation of PD will be censored at the date of last response assessment. DOR was categorized as CR+PR and CR.

6. Phase 2: Number of Participants With Response Rates in PSMB1 Positive and PSMB1 Negative [Baseline up to occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 802)]

7. Number of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Baseline up to 30 days after last dose of study drug (approximately up to Day 832)]

8. Lead-in Dose Finding Phase: Cmax: Maximum Observed Plasma Concentration for Ixazomib [Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose]

9. Lead-in Dose Finding Phase: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib [Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose]

10. Lead-in Dose Finding Phase: AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for Ixazomib [Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose]

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 participants 18 years or older.

• Participants must have a pathologically confirmed diagnosis of non-Hodgkin lymphoma (NHL) (for the lead-in dose-finding phase) and FL (for phase 2).

• Participants must have radiographically or clinically measurable disease.

• Participants must be relapsed and/or refractory after at least 1 prior therapy (excluding radiation) with documented progressive disease at the time of enrollment.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

• Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.

• Male participants who agree to practice effective barrier contraception or agree to practice true abstinence.

• Voluntary written consent.

• Suitable venous access.

• Appropriate clinical laboratory values as defined in the protocol.

• Recovered from toxicities of prior anticancer therapy.

• If the trial proceeds to the second step on the basis of the tandem 2-step design, participants must be confirmed PSMB1 positive at the central laboratory before treatment.

Exclusion Criteria

• Peripheral neuropathy that is greater or equal to Grade 2 or Grade 1 with pain.

• Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.

• Autologous stem cell transplant within 6 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.

• Major surgery within 14 days before the first dose of study drug.

• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study drug.

• Comorbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the participants inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

• Evidence of current uncontrolled cardiovascular conditions including uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, unstable angina, New York Heart Association (NYHA) Class III or IV cardiac disease, or myocardial infarction within the past 6 months.

• Diarrhea greater than (>) Grade 1 on the basis of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.

• Systemic antineoplastic (including glucocorticoids > the equivalent of 15 mg of prednisone daily), experimental, or radiation therapy within 21 days before the first dose of study drug.

• Prior treatment with rituximab or other unconjugated antibody treatment within 42 days (21 days if clear evidence of progressive disease or immediate treatment is mandated).

• Treatment with radioimmunoconjugates or toxin immunoconjugates within 12 weeks before the first dosing of study treatment.

• Systemic treatment with strong inhibitors of Cytochrome P450 1A2 (CYP1A2) or Cytochrome P450 3A (CYP3A), or strong CYP3A inducers within 14 days before the first dose of IXAZOMIB - Ongoing systemic therapy with corticosteroids.

• Central nervous system (CNS) involvement that is clinically uncontrolled or newly diagnosed in the last 4 months.

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

• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ.

• Platelet transfusions within 3 days before the 1st dose of study drug.

• Inability to swallow capsules, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medication for 2 hours before and 1 hour after dose of IXAZOMIB - Known allergy to boron or excipients in the formulation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Boston	Massachusetts	United States
2		New York	New York	United States
3		Nashville	Tennessee	United States
4		Houston	Texas	United States
5		Gent		Belgium
6		Leuven		Belgium
7		Wilrijk		Belgium
8		Montreal	Quebec	Canada
9		London		United Kingdom
10		Manchester		United Kingdom
11		Newcastle Upon Tyne		United Kingdom
12		Plymouth		United Kingdom
13		Southampton		United Kingdom
14		Sutton		United Kingdom

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01939899
• Other Study ID Numbers: C16017; 2013-002302-32; U1111-1164-7551; 166547; REec-2016-2137; 13/EM/0373
• First Posted: Sep 11, 2013
• Last Update Posted: Oct 29, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Millennium Pharmaceuticals, Inc.: MLN9708; Lymphoma; IXAZOMIB
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Ixazomib

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 11 investigative sites in the United States, Belgium, Canada, United Kingdom and Italy from 31 October 2013 to 23 March 2017.
Pre-assignment Detail	Participants with follicular lymphoma (FL) prior to treatment were enrolled in this 2 phase study: Lead in dose finding phase in which maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ixazomib was evaluated and Phase 2 proteasome subunit beta type-1 (PSMB1) was done to evaluate the safety, efficacy, tolerability of ixazomib.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Period Title: Lead-in Dose Finding Phase
STARTED	3	7	6	0	0
COMPLETED	1	0	1	0	0
NOT COMPLETED	2	7	5	0	0
Period Title: Lead-in Dose Finding Phase
STARTED	0	0	0	12	1
COMPLETED	0	0	0	1	0
NOT COMPLETED	0	0	0	11	1

Baseline Characteristics

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative	Total
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.	Total of all reporting groups
Overall Participants	3	7	6	12	1	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.0 (6.56)	57.9 (11.13)	64.3 (7.71)	64.7 (11.73)	79.0 (NA)	64.2 (10.90)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 14.3%	1 16.7%	4 33.3%	1 100%	8 27.6%
Male	2 66.7%	6 85.7%	5 83.3%	8 66.7%	0 0%	21 72.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	3 100%	7 100%	6 100%	12 100%	0 0%	28 96.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 100%	1 3.4%
Region of Enrollment (participants) [Number]
Belgium	1 33.3%	2 28.6%	3 50%	3 25%	0 0%	9 31%
Canada	0 0%	1 14.3%	2 33.3%	0 0%	0 0%	3 10.3%
United Kingdom	0 0%	3 42.9%	1 16.7%	2 16.7%	0 0%	6 20.7%
Italy	0 0%	0 0%	0 0%	5 41.7%	0 0%	5 17.2%
United States	2 66.7%	1 14.3%	0 0%	2 16.7%	1 100%	6 20.7%
Smoking classification (Count of Participants)
Never smoked	2 66.7%	4 57.1%	5 83.3%	7 58.3%	1 100%	19 65.5%
Current smoker	0 0%	2 28.6%	0 0%	0 0%	0 0%	2 6.9%
Ex-smoker	1 33.3%	1 14.3%	1 16.7%	5 41.7%	0 0%	8 27.6%
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	170.0 (7.04)	175.0 (11.50)	169.2 (9.11)	168.8 (6.70)	157.5 (NA)	170.1 (8.77)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	76.1 (11.27)	85.8 (20.72)	85.3 (10.95)	78.7 (13.54)	82.4 (NA)	81.6 (14.45)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Overall Response Rate (ORR)
Description	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using the international Working Group criteria for participants CR: disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
Time Frame	Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies

Outcome Measure Data

Analysis Population Description

The response-evaluable population included all participants who received at least 1 dose of ixazomib, had measurable disease at baseline, and had at least 1 post baseline disease assessment.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Measure Participants	3	5	5	12	1
CR	0 0%	0 0%	0 0%	0 0%	0 0%
PR	0 0%	0 0%	0 0%	1 8.3%	0 0%
Stable Disease (SD)	1 33.3%	2 28.6%	2 33.3%	4 33.3%	0 0%
PD	2 66.7%	3 42.9%	3 50%	7 58.3%	1 100%

2. Secondary Outcome

Title	Lead-in Dose Finding Phase: Recommended Phase 2 Dose (RP2D)
Time Frame	Baseline up to Cycle 1 Day 28

Outcome Measure Data

Analysis Population Description

The dose limiting toxicity (DLT)- evaluable population included all participants who received all Cycle 1 doses of ixazomib and had completed Cycle 1 safety procedures, or experience a DLT in Cycle 1 in the lead-in dose finding phase of the study.

Arm/Group Title	Lead-in Dose Finding Phase: All Participants
Arm/Group Description	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
Measure Participants	16
Number [mg]	5.3

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death. Participants without documentation of PD will be censored at the date of last response assessment that is SD or better. Participants without response assessment will be censored at the date of first dose.
Time Frame	Time from the date of first dose of study treatment to the date of first documented PD or death (approximately up to Day 802)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population included all participants who received at least 1 dose of ixazomib in the phase 2 portion of the study or who received at least 1 dose of ixazomib and are treated at the RP2D in the lead-in dose finding phase of the study.

Arm/Group Title	Lead-in Dose Finding: Ixazomib 5.3 mg (RP2D)	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Measure Participants	7	12	1
Median (95% Confidence Interval) [months]	1.9	2.4	NA

4. Secondary Outcome

Title	Phase 2: Rate of Disease Control
Description	Rate of disease control is defined as percentage of participants who achieved a SD or better for greater than or equal to (>=) 6 months.
Time Frame	Baseline or until occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 805)

Outcome Measure Data

Analysis Population Description

The response-evaluable population included all participants who received at least 1 dose of ixazomib, had measurable disease at baseline, and had at least 1 post baseline disease assessment.

Arm/Group Title	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Measure Participants	12	1
Number (95% Confidence Interval) [percentage of participants]	16.7 556.7%	NA NaN

5. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR is defined as the time from the date of first dose of study treatment to the date of the first documentation of a PR or better response in a participant who responded.
Time Frame	Time from the date of first dose of study treatment to the date of first documented PR or better response or death (approximately up to Day 802)

Outcome Measure Data

Analysis Population Description

The response-evaluable population included all participants who received at least 1 dose of ixazomib, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Participants who were evaluable for this given measure at a given time point were included for this assessment.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Measure Participants	0	0	0	1	0
Median (95% Confidence Interval) [days]	560

6. Secondary Outcome

Title	Duration of Response (DOR)
Description	The DOR is defined as the time from the date of first documentation of a response to the date of first documented PD. Responders without documentation of PD will be censored at the date of last response assessment. DOR was categorized as CR+PR and CR.
Time Frame	Time from the date of first documentation of a response to the date of first documented PD (approximately up to Day 802)

Outcome Measure Data

Analysis Population Description

The response-evaluable population included all participants who received at least 1 dose of ixazomib, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Participants who were evaluable for this given measure at a given time point were included for this assessment.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Measure Participants	0	0	0	1	0
Median (95% Confidence Interval) [months]	0.0328542094

7. Secondary Outcome

Title	Phase 2: Number of Participants With Response Rates in PSMB1 Positive and PSMB1 Negative
Time Frame	Baseline up to occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 802)

Outcome Measure Data

Analysis Population Description

The biomarker population included all participants positive or negative for the PSMB1 biomarker and where the assay has passed quality control. Data will be derived from a baseline blood sample.

Arm/Group Title	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Measure Participants	12	1
Number [participants]	12 400%	1 14.3%

8. Secondary Outcome

Title	Number of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame	Baseline up to 30 days after last dose of study drug (approximately up to Day 832)

Outcome Measure Data

Analysis Population Description

The safety population included all enrolled participants who had received at least 1 dose of ixazomib.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Phase 2: PSMB1 Positive	Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
Measure Participants	3	7	6	12	1
TEAE	3 100%	7 100%	6 100%	11 91.7%	1 100%
SAE	1 33.3%	3 42.9%	4 66.7%	4 33.3%	1 100%

9. Secondary Outcome

Title	Lead-in Dose Finding Phase: Cmax: Maximum Observed Plasma Concentration for Ixazomib
Time Frame	Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description

The plasma pharmacokinetic (PK) analysis population included all participants enrolled in the lead-in dose finding phase that had sufficient dosing data and ixazomib concentration-time data. The PK analysis population where data at specified time points was available.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
Measure Participants	3	7	6
Cycle 1 Day 1	141.3333 (52.27173)	103.4717 (57.53181)	121.1167 (69.07212)
Cycle 1 Day 15	124.2667 (71.01840)	144.0667 (105.15884)	152.0667 (102.71131)

10. Secondary Outcome

Title	Lead-in Dose Finding Phase: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Time Frame	Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis population included all participants enrolled in the lead-in dose finding phase that had sufficient dosing data and ixazomib concentration-time data. The PK analysis population where data at specified time points was available.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
Measure Participants	3	7	6
Cycle 1 Day 1	1.0000	1.0000	1.0500
Cycle 1 Day 15	1.0000	0.7500	1.0000

11. Secondary Outcome

Title	Lead-in Dose Finding Phase: AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for Ixazomib
Time Frame	Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set where Cycle 1 Day 1 and 15 assessment were available. The PK analysis population included all participants enrolled in the lead-in dose finding phase that had sufficient dosing data and ixazomib concentration-time data. The PK analysis population where data at specified time points was available.

Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Lead-in Dose Finding Phase: Ixazomib 7.0 mg
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
Measure Participants	3	7	6
Cycle 1 Day 1	1265.0000 (332.34019)	1030.1429 (367.90326)	1680.3333 (656.01240)
Cycle 1 Day 15	2440.0000 (272.21315)	2007.0000 (986.30117)	3120.0000 (2503.83706)

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to Cycle 29)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Lead-in Dose Finding Phase: Ixazomib 4 mg		Lead-in Dose Finding Phase: Ixazomib 5.3 mg		Lead-in Dose Finding Phase: Ixazomib 7.0 mg		Phase 2: PSMB1 Positive		Phase 2: PSMB1 Negative
Arm/Group Description	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.		Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.		Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.		Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.		Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
All Cause Mortality
	Lead-in Dose Finding Phase: Ixazomib 4 mg		Lead-in Dose Finding Phase: Ixazomib 5.3 mg		Lead-in Dose Finding Phase: Ixazomib 7.0 mg		Phase 2: PSMB1 Positive		Phase 2: PSMB1 Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		3/7 (42.9%)		1/6 (16.7%)		0/12 (0%)		0/1 (0%)
Serious Adverse Events
	Lead-in Dose Finding Phase: Ixazomib 4 mg		Lead-in Dose Finding Phase: Ixazomib 5.3 mg		Lead-in Dose Finding Phase: Ixazomib 7.0 mg		Phase 2: PSMB1 Positive		Phase 2: PSMB1 Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		3/7 (42.9%)		4/6 (66.7%)		4/12 (33.3%)		1/1 (100%)
Cardiac disorders
Myocardial infarction	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/12 (16.7%)	2	0/1 (0%)	0
Vomiting	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
General disorders
Asthenia	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	2	1/12 (8.3%)	1	0/1 (0%)	0
Pyrexia	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/12 (0%)	0	1/1 (100%)	1
Local swelling	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Hepatobiliary disorders
Bile duct obstruction	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0
Infections and infestations
Bronchopulmonary aspergillosis	0/3 (0%)	0	1/7 (14.3%)	2	1/6 (16.7%)	2	0/12 (0%)	0	0/1 (0%)	0
Herpes zoster	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Respiratory tract infection	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0	0/1 (0%)	0
Bronchitis	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0	0/1 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Tumour pain	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction	0/3 (0%)	0	1/7 (14.3%)	2	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0
Vascular disorders
Orthostatic hypotension	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	Lead-in Dose Finding Phase: Ixazomib 4 mg		Lead-in Dose Finding Phase: Ixazomib 5.3 mg		Lead-in Dose Finding Phase: Ixazomib 7.0 mg		Phase 2: PSMB1 Positive		Phase 2: PSMB1 Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		7/7 (100%)		6/6 (100%)		11/12 (91.7%)		1/1 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	1/3 (33.3%)	1	1/7 (14.3%)	1	2/6 (33.3%)	4	3/12 (25%)	4	0/1 (0%)	0
Anaemia	1/3 (33.3%)	2	0/7 (0%)	0	3/6 (50%)	3	0/12 (0%)	0	0/1 (0%)	0
Neutropenia	0/3 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0	2/12 (16.7%)	2	0/1 (0%)	0
Eye disorders
Vision blurred	2/3 (66.7%)	2	1/7 (14.3%)	1	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/3 (33.3%)	1	4/7 (57.1%)	4	6/6 (100%)	10	5/12 (41.7%)	17	1/1 (100%)	1
Nausea	2/3 (66.7%)	5	3/7 (42.9%)	4	3/6 (50%)	7	5/12 (41.7%)	11	1/1 (100%)	1
Vomiting	2/3 (66.7%)	3	1/7 (14.3%)	1	4/6 (66.7%)	10	5/12 (41.7%)	16	1/1 (100%)	1
Abdominal pain	3/3 (100%)	3	0/7 (0%)	0	2/6 (33.3%)	2	3/12 (25%)	3	0/1 (0%)	0
Constipation	1/3 (33.3%)	1	1/7 (14.3%)	1	2/6 (33.3%)	2	1/12 (8.3%)	1	1/1 (100%)	1
Abdominal pain upper	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Haemorrhoids	2/3 (66.7%)	2	0/7 (0%)	0	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0
General disorders
Fatigue	1/3 (33.3%)	1	4/7 (57.1%)	5	3/6 (50%)	3	2/12 (16.7%)	3	0/1 (0%)	0
Asthenia	1/3 (33.3%)	1	1/7 (14.3%)	1	0/6 (0%)	0	4/12 (33.3%)	6	0/1 (0%)	0
Pyrexia	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	4/12 (33.3%)	11	0/1 (0%)	0
Oedema peripheral	1/3 (33.3%)	1	0/7 (0%)	0	2/6 (33.3%)	2	0/12 (0%)	0	0/1 (0%)	0
Chills	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Infections and infestations
Nasopharyngitis	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	1/12 (8.3%)	2	0/1 (0%)	0
Urinary tract infection	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/12 (16.7%)	2	0/1 (0%)	0
Injury, poisoning and procedural complications
Fall	0/3 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	2	1/12 (8.3%)	1	0/1 (0%)	0
Investigations
Neutrophil count decreased	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/12 (16.7%)	2	0/1 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	3/3 (100%)	3	2/7 (28.6%)	2	3/6 (50%)	3	2/12 (16.7%)	2	0/1 (0%)	0
Hypokalaemia	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	2/12 (16.7%)	2	0/1 (0%)	0
Arthralgia	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Back pain	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Musculoskeletal chest pain	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Pain in extremity	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	2	0/1 (0%)	0
Nervous system disorders
Headache	1/3 (33.3%)	1	1/7 (14.3%)	1	1/6 (16.7%)	1	2/12 (16.7%)	3	0/1 (0%)	0
Dizziness	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Dysgeusia	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Neuropathy peripheral	0/3 (0%)	0	1/7 (14.3%)	2	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Psychiatric disorders
Insomnia	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	1	2/7 (28.6%)	2	3/6 (50%)	3	1/12 (8.3%)	5	0/1 (0%)	0
Dyspnoea	0/3 (0%)	0	2/7 (28.6%)	2	1/6 (16.7%)	1	1/12 (8.3%)	4	0/1 (0%)	0
Epistaxis	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis acneiform	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Dry skin	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Night sweats	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0
Pruritus	1/3 (33.3%)	2	1/7 (14.3%)	1	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0
Rash maculo-papular	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	0/12 (0%)	0	0/1 (0%)	0
Vascular disorders
Hypotension	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1	0/1 (0%)	0
Orthostatic hypotension	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0	0/1 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.