Chronic Administration of Diosmectite (SMECTA®) in Subjects With Chronic Diarrhoea

Assessment of Elemental Impurities Level After Chronic Administration of Diosmectite (SMECTA®) in Subjects With Chronic Diarrhoea

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03045926

Enrollment

Registered

2017-02-08

Start date

2016-08-31

Completion date

2017-05-09

Last updated

2019-04-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Functional Diarrhea of Unknown Origin

Brief summary

The main purpose of this study is to assess the concentration of elemental impurities in blood and urine after chronic administration of Smecta® in subjects with chronic functional diarrhoea. For exploratory purposes, the potential effects of diosmectite on bowel microbiote composition will be investigated.

Interventions

DRUGDiosmectite (Smecta®)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Intervention model description

The study is interventional Phase 1 without individual benefit.

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Inclusion criteria

* Male or female subjects, between 18 and 60 years old inclusive, BMI between 19 and 32 kg/m2 inclusive (minimum body weight of 50 kg at screening). * Functional chronic diarrhoea defined as loose or watery stools occurring in at least 75% of stools for the last 3 months (with symptom onset at least 6 months before diagnosis).

Exclusion criteria

* No history of suspected organic or drug induced cause to chronic diarrhoea.

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood lead levels (BLL) were defined as the average between the available screening and pre-dose (Day-1) values. Values below the limit of detection (LOD) or below the lower limit of quantification (LLOQ) were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in BLL during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in BLL during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Secondary

Measure	Time frame	Description
Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood arsenic concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood arsenic concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood arsenic concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood barium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood barium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood barium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood cadmium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood cadmium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood cadmium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood cobalt concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood cobalt concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood cobalt concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood mercury concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood mercury concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood mercury concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood nickel concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood nickel concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood nickel concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Mean Change From Baseline in Urine Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine lead levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine lead levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 125.	Baseline blood aluminium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood aluminium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood aluminium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Mean Change From Baseline in Urine Arsenic Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine arsenic levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine arsenic levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
Mean Change From Baseline in Urine Barium Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine barium levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine barium levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
Mean Change From Baseline in Urine Cadmium Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine cadmium levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine cadmium levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
Mean Change From Baseline in Urine Cobalt Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine cobalt levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine cobalt levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
Mean Change From Baseline in Urine Mercury Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine mercury levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine mercury levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
Mean Change From Baseline in Urine Nickel Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine nickel levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine nickel levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
Mean Change From Baseline in Urine Aluminium Levels During the Treatment Period and Post-treatment Follow-up Period	Screening and pre-dose Day -1 up to Day 95.	Baseline urine aluminium levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine aluminium levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.

Countries

Netherlands, United Kingdom

Participant flow

Recruitment details

35 subjects with chronic functional diarrhoea were enrolled into this open label study in 2 study centres in the Netherlands and United Kingdom. The first subject started 24 August 2016 and last subject completed 9 May 2017.

Pre-assignment details

73 subjects were screened for inclusion in the study, 38 subjects failed screening, and 35 met all the inclusion and none of the exclusion criteria. All 35 subjects received treatment with study medication.

Participants by arm

Arm	Count
Smecta® Powder Subjects received Smecta® (3 g of diosmectite), ingested three times a day, in the morning, at noon and in the evening, every day from Day 1 to Day 35 before meals in the fasting state. Subjects were followed up for up to 3 months after the last dose of Smecta® administered on Day 35, up to Day 125.	35
Total	35

Baseline characteristics

Characteristic	Smecta® Powder
Age, Continuous	36.4 years STANDARD_DEVIATION 12.9
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	35 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	33 Participants
Sex: Female, Male Female	15 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 35
other Total, other adverse events	30 / 35
serious Total, serious adverse events	0 / 35

Outcome results

Primary

Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period

Baseline blood lead levels (BLL) were defined as the average between the available screening and pre-dose (Day-1) values. Values below the limit of detection (LOD) or below the lower limit of quantification (LLOQ) were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in BLL during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in BLL during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Population: The Intention-to-Treat (ITT) population consisted of all subjects who received at least one dose of study medication and who had one pre-dose BLL and at least one post-dose BLL. Subjects with data available at the timepoints analysed are presented.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	1.197 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	0.120 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	0.306 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	0.095 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	0.359 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	0.308 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	-0.096 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	0.836 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	2.539 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	4.722 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	6.094 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	6.900 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	6.866 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	7.379 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	6.865 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	7.328 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	8.248 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	6.876 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	7.632 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up)	3.907 nanograms per millilitre (ng/mL)
Smecta® Powder	Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	-0.101 nanograms per millilitre (ng/mL)

Secondary

Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period

Baseline blood aluminium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood aluminium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood aluminium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Population: The ITT population consisted of all subjects who received at least one dose of study medication and who had one pre-dose BLL and at least one post-dose BLL. Subjects with data available at the timepoints analysed are presented.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	-14.958 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	-6.225 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	-1.688 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	-9.392 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	-14.181 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	-14.181 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	-11.733 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	-15.474 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	-2.884 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	-14.958 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	-7.142 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	-14.958 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	-13.708 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	-13.708 ng/mL

Secondary

Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period

Baseline blood arsenic concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood arsenic concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood arsenic concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	0.037 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	-0.029 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	-0.003 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	-0.067 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	-0.059 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	0.034 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	0.027 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	0.312 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	0.484 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	0.429 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	0.640 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	0.461 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	0.462 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	0.415 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	0.420 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	0.361 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	0.359 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	0.350 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up)	0.507 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	0.295 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	0.051 ng/mL

Secondary

Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period

Baseline blood barium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood barium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood barium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	0.229 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	1.300 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	4.229 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	0.341 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	0.371 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	0.114 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	0.114 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	0.340 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	0.471 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	0.114 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	1.086 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	0.229 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	0.563 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	0.114 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	6.609 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up)	0.660 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	2.423 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	3.023 ng/mL

Secondary

Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period

Baseline blood cadmium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood cadmium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood cadmium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	0.017 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	-0.002 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	0.020 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	-0.029 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	0.006 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	-0.003 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	0.015 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	-0.004 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	0.025 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	-0.006 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	0.033 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	-0.009 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	-0.023 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	-0.020 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	-0.009 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	-0.038 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	-0.025 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	-0.035 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up)	0.034 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	-0.073 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	-0.110 ng/mL

Secondary

Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period

Baseline blood cobalt concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood cobalt concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood cobalt concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	0.006 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	0.006 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	-0.019 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	-0.007 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	0.019 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	0.019 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	0.019 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	0.032 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	0.084 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	0.046 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	0.045 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	0.045 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	0.045 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	0.032 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	0.019 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	0.045 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	0.032 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	0.019 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up)	0.084 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	-0.006 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	0.006 ng/mL

Secondary

Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period

Baseline blood mercury concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood mercury concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood mercury concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	-0.017 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	-0.005 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	-0.013 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	0.013 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	0.012 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	-0.020 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	0.015 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	0.098 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	0.155 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	0.019 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	-0.041 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	-0.076 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	-0.008 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	-0.046 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	-0.085 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	-0.091 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	-0.113 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	-0.085 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up)	0.064 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	0.080 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	0.112 ng/mL

Secondary

Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period

Baseline blood nickel concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in blood nickel concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning. The absolute mean change from baseline in blood nickel concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).

Time frame: Screening and pre-dose Day -1 up to Day 125.

Arm	Measure	Group	Value (MEAN)
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 1	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 1	-0.257 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 1	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 1	0.132 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 1	0.129 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 1	0.129 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 2	0.714 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 8	-0.257 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 15	-0.257 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 22	0.265 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, First Dose Day 29	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	2 hours post-dose, First Dose Day 35	0.129 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Second Dose Day 35	-0.257 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Second Dose Day 35	-0.386 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Pre-dose, Third Dose Day 35	0.129 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	3 hours post-dose, Third Dose Day 35	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	6 hours post-dose, Third Dose Day 35	0.000 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 36 morning	-0.257 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 65 (follow-up)	-0.514 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 95 (follow-up)	0.643 ng/mL
Smecta® Powder	Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period	Day 125 (End of Study)	1.414 ng/mL

Secondary

Mean Change From Baseline in Urine Aluminium Levels During the Treatment Period and Post-treatment Follow-up Period

Baseline urine aluminium levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values. The absolute mean change from baseline in urine aluminium levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.

Time frame: Screening and pre-dose Day -1 up to Day 95.