G-PUR® for Reduced Lead Bioavailability

Study Overview
=================
Brief Summary
-----------------
This is a prospective, randomized, placebo-controlled, double blind, parallel-arm study in a two-staged approach that will assess the effect of two different doses of G-PUR® on enteral lead absorption in healthy adults using a stable lead isotopic tracer (204Pb).

Official Title
-----------------
A Randomized, Placebo-controlled, Double-blind Study to Evaluate the Effect of G-PUR® on Enteral Lead Isotope 204Pb-absorption

Conditions
-----------------
Lead Exposure

Intervention / Treatment
-----------------
* Device: G-PUR® 2x 2.0 g oral suspension
* Device: G-PUR® 1x 2.0 g oral suspension
* Device: Placebo oral suspension


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and female subjects Age 18-45 years BMI 19-27 for males and BMI 17-25 for female Blood lead (PbB) concentration < 40 μg/l Serum ferritin concentration within the sex-specific normal range, i.e. ≥ 15 - 150 ng/ml for women and 30 - 400 ng/ml for men Presence of scalp hair with a minimum length of 5 mm and willingness to remove 5 single hairs with hair roots at end of study visit Subject is in good clinical and mental health as established by medical history and physical examination Stable eating habits, within one month before the start of the study Subject agrees to be compliant for study related diet schedule Women of childbearing potential agree to use adequate birth control methods during the study (for all females, negative pregnancy test at screening and at Visit 3 before dosing of IMD is required. Females of childbearing potential must use adequate contraception during the entire study period. Acceptable methods of contraception include: oral contraceptives, intrauterine device, female or male condoms with spermicide, diaphragm with spermicide, contraceptive medication patch, contraceptive medication implant, contraceptive medication injection, abstinence, or surgical sterilization more than 3 months before randomization. Written informed consent Exclusion Criteria: Pregnancy and breastfeeding Lack of willingness or capacity to co-operate appropriately Regular use of medications or iron supplements in the previous 2 months except intake of contraceptives Planning to shave head during study History of malignancies within the past two years or on current anticancer treatment History of gastrointestinal pathology such as gastritis, gastric ulcers, irritable bowel disease, inflammatory bowel disease, chronic constipation History of diarrhoea within the past 14 days of screening History of gastrointestinal surgery with exception of appendectomy History of chronic autoimmune disease requiring treatment within the past two months of screening Known diabetes mellitus I or II or Hba1c >6.5% Known symptomatic food allergies Any clinically relevant laboratory abnormalities in screening test Alcohol, cigarette or drug abuse Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study Presence of any condition that impacts compliance with the study procedures Use of any regular medication (prescription or over the counter) for prevention or treatment of any medical condition Use of any investigational or non-registered product (drug or device) within 30 days preceding the first study product administration, or planned use during the study period Employee at the study site, spouse/partner or relative of any study staff (e.g. investigator, sub-investigators, or study nurse) or relationship to the sponsor IMD should not be applied to patients that suffer from aluminium and/or silicon hypersensitivity or in case of renal failure that requires dialysis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 2 x 2.0 g G-PUR® oral suspension<br> | Device: G-PUR® 2x 2.0 g oral suspension<br>* Cohort 1: 2 g G-PUR® powder mixed with 100 ml water in an opaque drinking bottle will be orally administered before and immediately after 204Pb intake<br>|
| Experimental: Cohort 2: 1 x 2.0 g G-PUR® oral suspension<br> | Device: G-PUR® 1x 2.0 g oral suspension<br>* Cohort 2: 2 g G-PUR® powder mixed with 100 ml water in an opaque drinking bottle will be orally administered before 204Pb intake and 100 ml water (placebo) in an opaque drinking bottle immediately after 204Pb intake<br>|
| Placebo Comparator: Cohort 3: Placebo oral suspension<br> | Device: Placebo oral suspension<br>* Cohort 3: 100 ml of water in an opaque drinking bottle will be orally administered immediately before and after 204Pb intake<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 204PbB Cmax normalized for total PbB | Cmax of 204PbB normalized for total natural PbB levels after intake of 204Pb-enriched water | 216 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of (S)ADE | Incidence of (serious) adverse device effects | 216 hours | 
| Plasma PK parameters - AUC0-t of 204PbB | The observed area under the blood concentration versus time curve between time 0 and the time point of the last quantifiable concentration, calculated using the trapezoidal rule method | 216 hours | 
| Plasma PK parameters - tmax of 204PbB | Time to reach the peak concentration: The sampling time at which Cmax was observed | 216 hours | 
| 204Pb concentrations in 24-hour urine | Measurement of 204Pb isotope tracer concentrations in 24-hour urine after intake of 204Pb enriched water | 24 hours | 
| 204Pb in single hairs | Lead isotope tracer (204Pb) distribution and ratio in single hairs | 9 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Blood/Urine/Hair lead, Lead uptake & Lead bioavailability