Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Optimization of Bioavailability From Iron Supplements: Examinations of Different Supplementation Regimens Including Hepcidin Profiles
Brief Summary: Iron deficiency (ID) with or without anaemia (IDA) is a major public health problem worldwide, especially in women of reproductive age and young children. Iron supplementation is an effective strategy to prevent and treat ID and IDA. There is a lack of data on iron bioavailability from different supplementation regimens and how to optimize bioavailability in a cost-effective and patient-friendly way. The present study will test whether the fractional and total iron absorption from iron supplements (60 mg) administered daily for 14 days differs from that of iron supplements (60 mg) administered every second day for 28 days. The prevailing serum hepcidin concentration (SHep) is the major determinant of iron absorption and erythrocyte iron utilization. Therefore we will monitor SHep during the whole supplementation period. We hypothesize that the fractional and total iron absorption from the daily administration of 60 mg is lower than that from the administration on every second day due to increased SHep levels when supplements are administered daily.

The study will provide important insights about the optimization of iron bioavailability from different supplementation regimens including the performance of SHep, a key regulator of human iron metabolism.


Options:
A: Inclusion Criteria:

* Male or female subject's ≥ 18 years of age, able to give informed consent to the study.
* Fibromyalgia diagnosis based on The 2011 modification of the American College of Rheumatology (ACR) 's 2010 preliminary criteria for diagnosing fibromyalgia (2011ModCr)
* A baseline score ≥ 60 on the FIQR
* Subject's current medications to treat fibromyalgia, including pain medicines, anti-depressants, sleep medications must be on a stable dose for at least 30 days.
* Subject's current narcotic medication must be on a stable dose for at least 30 days prior to randomization
* Subjects at risk for pregnancy must have a negative pregnancy test at baseline and be practicing an acceptable form of birth control: have had a hysterectomy or tubal ligation, or otherwise be incapable of pregnancy, or have practiced any of the following methods of contraception for at least one month prior to study entry: hormonal contraceptives, spermicide and barrier, intrauterine device, partner sterility.

Exclusion Criteria:

* Parenteral iron use within 4 weeks prior to screening.
* History of \> 10 blood transfusions in the past 2 years.
* Anticipated need for blood transfusion during the study.
* Known hypersensitivity reaction to any component of Injectafer® (Ferric Carboxymaltose).
* Current or acute or chronic infection other than viral upper respiratory tract infection
* Malignancy (other than basal or squamous cell skin cancer or the subject has been cancer free for ≥ 5 years).
* Active inflammatory arthritis (e.g. rheumatoid arthritis, SLE).
* Pregnant or lactating women.
* Severe peripheral vascular disease with significant skin changes.
* Seizure disorder currently being treated with medication.
* Baseline ferritin ≥ 50 ng/mL.
* Baseline TSAT ≥ 20%.
* History of hemochromatosis or hemosiderosis or other iron storage disorders.
* Known positive hepatitis with evidence of active disease.
* Hemoglobin greater than the upper limit of normal.
* Calcium or phosphorous outside the normal range.
* Known positive hepatitis B antigen (HBsAg) or hepatitis C viral antibody (HCV) with evidence of active hepatitis (i.e., AST/ALT greater than the upper limit of normal).
* Known positive HIV-1/HIV-2 antibodies (anti-HIV)
* Received an investigational drug within 30 days before randomization.
* Chronic alcohol or drug abuse within the past 6 months.
* Any other pre-existing laboratory abnormality, medical condition or disease which in view of the investigator participation in this study may put the subject at risk.
* Subject unable to comply with the study requirements.
B: Inclusion Criteria:

* Female, 18 to 45 years old,
* Serum ferritin levels \</=25 µg/L,
* Normal body Mass Index (18.5-26.5 kg/m2),
* Body weight \<80 kg,
* Signed informed consent

Exclusion Criteria:

* Anaemia (Hb \< 8.0 g/dL),
* Elevated c-reactive protein or alpha1-glycoprotein concentrations \>5.0 mg/L, \>1.0 g/L, respectively,
* Any metabolic, gastrointestinal kidney or chronic disease such as diabetes, renal failure, hepatic dysfunction, hepatitis, hypertension, cancer or cardiovascular diseases (according to the participants own statement),
* Continuous/long-term use of medication during the whole studies (except for contraceptives),
* Consumption of mineral and vitamin supplements within 2 weeks prior to 1st supplement administration,
* Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 4 months,
* Earlier participation in a study using stable iron isotopes,
* Known hypersensitivity or allergy to iron supplements,
* Women who are pregnant or breast feeding,
* Intention to become pregnant during the course of the studies,
* Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
* Known or suspected non-compliance, drug or alcohol abuse,
* Inability to follow the procedures of the studies, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Participation in another study with investigational drug within the 30 days preceding and during the present studies,
* Enrolment of the investigator, his/her family members, employees and other dependent persons
C: Inclusion Criteria:

* In New York Heart Association (NYHA) II-III functional class due to stable symptomatic chronic heart failure (CHF)
* Left ventricular ejection fraction (LVEF) 40% or lower for patients in NYHA II and 45% or lower in NYHA III
* Screening haemoglobin (Hb) at least 9.5 g/dL but below or equal to 13.5 g/dL (average of 2 haemoglobin concentrations)
* Screening ferritin below 100 µg/L, or below 300 µg/L when transferrin saturation (TSAT) is below 20%

Exclusion Criteria:

* History of acquired iron overload.
* Known active infection, clinically significant bleeding, active malignancy.
* Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST)
* Anaemia due to reasons other than iron deficiency
* Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months).
* History of erythropoietin, i.v. or oral iron therapy, and blood transfusion in previous 12 weeks and/or such therapy planned within the next 6 months.
* Unstable angina pectoris as judged by the investigator, clinically significant uncorrected valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, poorly controlled fast atrial fibrillation or flutter, poorly controlled symptomatic brady- or tachyarrhythmias.
* Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack or stroke within the last 3 months.
* Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months.
D: Inclusion Criteria:

* Signed informed consent prior to study specific procedures.
* Premenopausal, regularly menstruating women.
* Age ≥18 years.
* Body weight between 50 and 90 kg.
* Haemoglobin ≥115 g/L.
* Iron deficiency at screening defined as follows:
* S-ferritin level \<50 ng/mL, AND, TfS \<20%, OR,
* S-ferritin level \<15 ng/mL.
* Serum C-reactive protein:
* \<5 mg/L if not on oral contraception, OR,
* \<20 mg/L if use of oral contraception.
* Minimum total score of 5 on the Piper Fatigue Scale (PFS) (mean of items 2 to 23).
* Negative pregnancy test (serum human chorionic gonadotropin (hCG) at screening.
* Normal levels of vitamin B12 and folic acid at screening.
* Adequate contraception during the study period and for 1 month following study completion.
* Availability and willingness to complete all study visits and procedures per protocol.

Exclusion Criteria:

* Haemoglobin level \<115 g/L.
* Haemoglobinopathy.
* Haemochromatose.
* Major depressive disorder based on Patient Health Questionnaire (PHQ-9) (5 items with scores ≥2; one of which corresponds to question number 1 or 2).
* Any active or unstable concurrent medical condition (e.g., cancer, renal dysfunction, liver dysfunction (aspartate aminotransferase (AST); alanine aminotransferase (ALT) \>3-fold upper limit), angina (Class IV).
* Known human immunodeficiency virus/acquired immunodeficiency syndrome, hepatitis B virus or hepatitis C virus infection.
* Chronic inflammatory disease (e.g., rheumatoid arthritis; inflammatory bowel disease).
* Documented history of clinically significant level of sleep apnoea defined as 5 or more episodes per hour of any type of apnoea.
* Intake of concurrent medications that could interfere with physical or mental performance (e.g., antidepressive, antihistamines, narcotic or any chemotherapeutic agents known to cause drowsiness).
* Important recent weight loss (\>10% within the past month).
* Body weight \<50 kg or \>90 kg.
* Thyroid dysfunction, thyroid stimulating hormone \>4 μU/mL.
* Intake of iron preparations 4 weeks prior to screening.
* Use of gestagens e.g., Implanon, Mirena, Depo-Provera for menstruation repression (see Section 7.7, Prohibited Therapy or Concomitant Treatment, page 35).
* Known hypersensitivity to FCM or to any other iron preparation.
* Pregnancy (positive hCG test at screening) or breast feeding.
* Participation in any other interventional trial within 4 weeks prior to screening.
* Inability to fully comprehend and/or perform study procedures or provide written consent in the Investigator's opinion.
* Subject is not using adequate contraceptive precautions during the study and for up to 1 month after the last dose of the study medication. A highly effective method of birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner.
* Subject previously has entered this study.
* Subject will not be available for follow-up assessments.

Answer: B