Magnesium Oxide in Treating Postmenopausal Women With Hot... | NCT01439945

ID	Type	Description
NCCTG-N10C2
CDR0000711021	Registry Identifier	PDQ (Physician Data Query)
NCI-2011-03537	Registry Identifier	CTRP (Clinical Trials Reporting System)

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

Primary

Evaluate the efficacy of magnesium oxide on hot flashes in women with a history of breast cancer.

Secondary

Evaluate the side-effect profile of magnesium oxide in this study population.
Evaluate the effect of magnesium oxide on the secondary outcomes hot flash frequencies, hot flash severities, toxicities (including diarrhea), and hot flash-related daily interference on activities.
Evaluate the effect of magnesium oxide on the change of magnesium level (for the first 150 patients).

OUTLINE: This is a multicenter study. Patients are stratified according to age (18-49 years vs ≥ 50 years), current tamoxifen and/or selective estrogen receptor modulator (yes vs no), current aromatase inhibitor (yes vs no), and daily frequency of hot flashes (4-9 vs ≥ 10). Patients are randomized to 1 of 4 treatment arms.

Arm I: Patients receive a low-dose of magnesium oxide orally (PO) daily (QD).
Arm II: Patients receive a high-dose of magnesium oxide PO QD.
Arm III: Patients receive a low-dose of placebo PO QD.
Arm IV: Patients receive a high-dose of placebo PO QD. In all arms, treatment continues for 8 weeks in the absence of unacceptable toxicity.

Some patients may continue or crossover to receive magnesium for 4 more weeks.

Patients complete the Hot Flash Diary daily for 9 weeks beginning 1 week before treatment. They also complete the Symptom Experience Questionnaire, the Profile of Mood States (POMS), and Hot Flash-Related Daily Interference Scale (HFRDIS) questionnaires periodically during study treatment.

Patients undergo blood sample collection at baseline and at the end of weeks 5 and 9 for serum magnesium level analysis.

Label	Type	Description	Intervention Names
Arm I	Experimental	Patients receive a low-dose of magnesium oxide orally (PO) daily (QD).	Drug: magnesium oxide
Arm II	Experimental	Patients receive a high-dose of magnesium oxide PO QD.	Drug: magnesium oxide
Arm III	Placebo Comparator	Patients receive a low-dose of placebo PO QD.	Other: placebo
Arm IV	Placebo Comparator	Patients receive a high-dose of placebo PO QD.	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
magnesium oxide	Drug	Given PO	Arm I Arm II
placebo

Measure	Description	Time Frame
The Intra-patient Changes of Weekly Hot Flash Activity From Baseline During the Treatment Period.	The primary endpoint is the intra-patient changes of weekly hot flash activity from baseline during the treatment period. The hot flash activity will be measured by the weekly average hot flash score, which is a composite entity of both frequency and severity of hot flashes. The hot flash severity is graded from 1 to 4 (1=mild, 2=moderate, 3=severe, and 4=very severe). The daily hot flash score is computed by multiplying the mean grade of severity by the frequency during every 24 hour period. Therefore, a score of zero is the lowest possible score and can be interpreted as having no hot flashes. The weekly hot flash score was calculated by adding all scores for the week. The mean Hot Flash Score for each week for each group is reported and a repeated measures analysis is reported comparing each dose level group to the Placebo group.	Baseline to Week 8

Measure	Description	Time Frame
Weekly Frequency of Hot Flashes as Measured by the Hot Flash Diary During the Treatment Period	As part of the Hot Flash Diary, the number of hot flashes was recorded for each patient for each week. For this endpoint, the mean number of hot flashes for each group is reported. A repeated measure analysis comparing each dose level group and the Placebo is reported.	Baseline to Week 8

Eligibility Module

Eligibility Criteria

DISEASE CHARACTERISTICS:

Women with a history of breast cancer (currently without malignant disease)
Bothersome hot flashes (defined by their occurrence ≥ 28 times per week and of sufficient severity to make the patient desire therapeutic intervention)
Presence of hot flashes for ≥ 30 days prior to study registration
Willingness to provide the biologic specimens as required by the protocol
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Women who are postmenopausal as defined by absence of a period in the past 12 months or bilateral oophorectomy
- Women with at least one ovary but without a uterus should be deemed postmenopausal by either age over 55 or a combination of estrogen within a postmenopausal range (per local lab) and FSH over 40 mIU/mL
- No women of childbearing potential or who are premenopausal
Creatinine clearance > 30 mL/min
Ability to complete questionnaire(s) by themselves or with assistance
ECOG performance status 0 or 1
No history of allergic or other adverse reaction to magnesium
No diabetes
No patients with conditions that are implicated in decreased absorption of magnesium (e.g., Crohn disease, ETOH abuse)
No patients who have diarrhea where magnesium might make it worse (per provider discretion)

PRIOR CONCURRENT THERAPY:

None of the following current (≤ 28 days prior to registration) or planned therapies (tamoxifen, raloxifene, or aromatase inhibitors are allowed, but the patient must have been on a constant dose for ≥ 28 days and must not be expected to stop the medication during the study period):
- Antineoplastic chemotherapy (trastuzumab or lapatinib are allowed)
- Androgens
- Estrogens (any delivery route)
- Progestational agents
No prior use of magnesium for hot flashes
No current or planned use of gabapentin (for any reasons) or antidepressants (for any reasons) or other agents for treating hot flashes (except stable dose of vitamin E is allowed as long as it was started > 30 days prior to study registration and are to be continued through the study period; soy is allowed, if it is planned to be continued at the same dose during the study period)
No current use of magnesium for any indication (except one standard multiple vitamin dose is allowed per day)
Not taking diuretics, corticosteroids, bile acid sequestrants, and other prescription and over-the-counter medications that may affect magnesium levels
No current (≤ 7 days prior to registration) or planned use of other non-drug therapies for managing hot flashes, such as acupuncture or yoga (use of these therapies for other reasons is allowed)

Name	Affiliation	Role
Charles L. Loprinzi, MD	Mayo Clinic	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital		Fairbanks	Alaska	99701	United States

ID	Title	Description
FG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Intra-patient Changes of Weekly Hot Flash Activity From Baseline During the Treatment Period.

The primary endpoint is the intra-patient changes of weekly hot flash activity from baseline during the treatment period. The hot flash activity will be measured by the weekly average hot flash score, which is a composite entity of both frequency and severity of hot flashes.

The hot flash severity is graded from 1 to 4 (1=mild, 2=moderate, 3=severe, and 4=very severe). The daily hot flash score is computed by multiplying the mean grade of severity by the frequency during every 24 hour period. Therefore, a score of zero is the lowest possible score and can be interpreted as having no hot flashes. The weekly hot flash score was calculated by adding all scores for the week.

The mean Hot Flash Score for each week for each group is reported and a repeated measures analysis is reported comparing each dose level group to the Placebo group.

All patients that began protocol treatment and completed the Hot Flash Diary were included in this analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline to Week 8

ID	Title	Description
OG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG001	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG002	Placebo	Patients registered to the High Dose Placebo and Low Dose Placebo are combined for treatment analysis. Week 2: Patients take one placebo tablets orally (PO) daily (QD). Week 3: Patients take two placebo tablets daily (QD). Weeks 4-9: Patients take two or three placebo tablets daily (QD).

Units	Counts
Participants	OG00088 OG00188 OG00291

Title

Denominators

Categories

Baseline

- ParticipantsOG00081
- ParticipantsOG00181
- ParticipantsOG00283

Title	Measurements

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		ANOVA	Weekly hot flash score was treated as a repeated measure for each patient.	0.13														Superiority or Other
OG001 OG002		ANOVA	Weekly hot flash score was treated as a repeated measure for each patient.

Secondary

Weekly Frequency of Hot Flashes as Measured by the Hot Flash Diary During the Treatment Period

As part of the Hot Flash Diary, the number of hot flashes was recorded for each patient for each week. For this endpoint, the mean number of hot flashes for each group is reported. A repeated measure analysis comparing each dose level group and the Placebo is reported.

All patients that began protocol treatment and completed the Hot Flash Diary were included in this analysis.

Posted

Mean

Standard Deviation

number of hot flashes

Baseline to Week 8

ID	Title	Description
OG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG001	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG002	Placebo

Secondary

Frequency and Maximum Grade of Adverse Events Reported Via the CTCAE 4.0 During the Treatment Period.

Frequency and severity of adverse events reported by patients in weekly Symptom Experience Questionnaire and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.

All patients that started protocol treatment and were evaluated for adverse events are included in this analysis.

Posted

Count of Participants

Participants

Baseline to Week 8

ID	Title	Description
OG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG001	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG002	Placebo

Secondary

The Change of Severity of Symptoms as Measured the Symptom Experience Questionnaire From Baseline to Treatment Termination

We will use the Symptom Experience Questionnaire (SEQ) to evaluate the specific impact of the study treatment on the effect hot flashes have on various life activities such as work, social, leisure and relationships. The questionnaire is 14 questions and is based on a 0="Not at all" to 10="As bad as it can be" scale. The change of severity of symptoms as measured by the SEQ from baseline to treatment termination will be first summarized by descriptive statistics as a percent change from baseline.

All patients that started treatment and completed the Symptom Experience Questionnaire at baseline and Cycle 9 were included in this analysis.

Posted

Median

Full Range

percentage change

Baseline to week 8

ID	Title	Description
OG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG001	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).

Secondary

The Change of Daily Interference as Measured by the Hot Flash Related Daily Interference Scale (HFRDIS) From Baseline to Treatment Termination.

We will use the Hot Flash Related Daily Interference Scale (HFRDIS) (SEQ) to evaluate the specific effect of hot flashes have on various life activities such as work, social, leisure and relationships while receiving treatment. The questionnaire is 10 questions and is based on a 0="Do not interfere" to 10="Completely interfere" scale. The weekly score is the summation of these 10 questions and therefore ranges from 0 to 100. The total change in severity of symptoms is calculated by subtracting the week 8 score from the baseline. Therefore, values below zero indicate a worsening of symptoms and values above zero indicate an improvement and has a maximum range of -100 to 100. A gatekeeper procedure, following a fixed-sequence hypothesis testing method, was used to examine the higher dose of magnesium vs. placebo first and then the lower dose of magnesium vs. placebo, if the former was statistically significant.

All patients that began treatment and completed the HFRDI questionnaire at baseline and week 8 were used in this analysis.

Posted

Median

Full Range

units on a scale

Baseline to week 8

ID	Title	Description
OG000	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG001

Secondary

The Intra-patient Changes of Magnesium Level From Baseline to the End of Treatment Period Between Magnesium Oxide and Placebo Arms.

The intra-patient changes of magnesium level from baseline to the end of treatment period between magnesium oxide and placebo arms will be compared using a repeated measures model.

Serum magnesium concentrations will be performed prior to study medication usage and during the last week of blinded study use. These will be obtained in the first 150 patients. Mean change in serum magnesium concentrations will be compared between the 3 study arms to determine whether there are any apparent changes in the patients receiving placebos vs the two magnesium doses.

All patients that started protocol treatment and had serum magnesium levels obtained at baseline and week 9 were included in this analysis.

Posted

Mean

Standard Deviation

mg/dL

Baseline to week 8

ID	Title	Description
OG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
OG001	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).	0	92	67	92
EG001	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).	1	93	40	93
EG002	Placebo	Patients registered to the High Dose Placebo and Low Dose Placebo are combined for treatment analysis. Week 2: Patients take one placebo tablets orally (PO) daily (QD). Week 3: Patients take two placebo tablets daily (QD). Weeks 4-9: Patients take two or three placebo tablets daily (QD).	0	92	31	92
EG003	Optional Continuation Phase	After the double blind phase patient questionnaire booklet has been completed and returned to the investigator, the patient will be told whether she was on magnesium or placebo. If the patient wishes to continue or start the magnesium, and healthcare provider approves that this is an appropriate option, she may be registered on the Optional Continuation Phase of the study. This phase will last up to 4 weeks of treatment following either 800 or 1200 mg/day treatment group.	0	116	40	116

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest pain - cardiac	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected93 at risk EG0020 events0 affected92 at risk EG0030 events0 affected116 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0015 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Endocrine disorders - Other, specify	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0021 events1 affected92 at risk EG003
Blurred vision	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0021 events1 affected92 at risk EG003
Eye disorders - Other, specify	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0015 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0007 events5 affected92 at risk EG0013 events2 affected93 at risk EG0023 events3 affected92 at risk EG003
Bloating	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00013 events2 affected92 at risk EG0011 events1 affected93 at risk EG0022 events1 affected92 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG000137 events52 affected92 at risk EG00166 events26 affected93 at risk EG00237 events21 affected92 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0021 events1 affected92 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0015 events3 affected93 at risk EG0025 events2 affected92 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0021 events1 affected92 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0025 events1 affected92 at risk EG003
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0012 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Hemorrhoidal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Hemorrhoids	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Lip pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0022 events1 affected92 at risk EG003
Mucositis oral	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0022 events1 affected92 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00021 events10 affected92 at risk EG0017 events6 affected93 at risk EG0024 events3 affected92 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected92 at risk EG0010 events0 affected93 at risk EG0022 events1 affected92 at risk EG003
Stomach pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG00011 events2 affected92 at risk EG0011 events1 affected93 at risk EG0025 events3 affected92 at risk EG003
Autoimmune disorder	Immune system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Infections and infestations - Other, specify	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Papulopustular rash	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0022 events1 affected92 at risk EG003
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Bruising	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0002 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Injury, poisoning and procedural complications - Other, specify	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0002 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Anorexia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0012 events2 affected93 at risk EG0022 events1 affected92 at risk EG003
Metabolism and nutrition disorders - Other, specify	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0008 events2 affected92 at risk EG0011 events1 affected93 at risk EG0021 events1 affected92 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0021 events1 affected92 at risk EG003
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0012 events2 affected93 at risk EG0020 events0 affected92 at risk EG003
Musculoskeletal and connective tissue disorder - Other, specify	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0021 events1 affected92 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG00110 events5 affected93 at risk EG0020 events0 affected92 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0022 events1 affected92 at risk EG003
Dizziness	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00014 events2 affected92 at risk EG0011 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0006 events4 affected92 at risk EG0012 events2 affected93 at risk EG0023 events3 affected92 at risk EG003
Agitation	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Depression	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0017 events2 affected93 at risk EG0024 events3 affected92 at risk EG003
Cystitis noninfective	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0014 events1 affected93 at risk EG0020 events0 affected92 at risk EG003
Dysmenorrhea	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Uterine pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected93 at risk EG0022 events1 affected92 at risk EG003
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003
Hot flashes	Vascular disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected92 at risk EG0011 events1 affected93 at risk EG0028 events2 affected92 at risk EG003
Hypertension	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected93 at risk EG0020 events0 affected92 at risk EG003

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D017616	Magnesium Compounds
D007287	Inorganic Chemicals
D010087	Oxides
D017601	Oxygen Compounds

ID	Title	Description
BG000	Low Dose Magnesium Oxide (800 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
BG001	High Dose Magnesium Oxide (1200 mg/Day)	Week 2: Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD). Week 3: Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD). Weeks 4-9: Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).
BG002	Placebo	Patients registered to the High Dose Placebo and Low Dose Placebo are combined for treatment analysis. Week 2: Patients take one placebo tablets orally (PO) daily (QD). Week 3: Patients take two placebo tablets daily (QD). Weeks 4-9: Patients take two or three placebo tablets daily (QD).
BG003	Total	Total of all reporting groups