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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002111-18 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diosmectite (Smecta®) | Experimental | 5 weeks of diosmectite 3g, 3 times daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Diosmectite (Smecta®) | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Screening and pre-dose Day -1 up to Day 125. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Health Sciences | Groningen | 9728NZ | Netherlands | |||
| MAC Clinical Research Limited |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35151268 | Derived | Da Silva K, Guilly S, Thirion F, Le Chatelier E, Pons N, Roume H, Quinquis B, Ehrlich SD, Bekkat N, Mathiex-Fortunet H, Sokol H, Dore J. Long-term diosmectite use does not alter the gut microbiota in adults with chronic diarrhea. BMC Microbiol. 2022 Feb 12;22(1):54. doi: 10.1186/s12866-022-02464-7. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Smecta® Powder | Subjects received Smecta® (3 grams [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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Baseline characteristics are presented for the Safety population which consisted of all subjects who received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 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). | 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. | Posted | Mean | 95% Confidence Interval | nanograms per millilitre (ng/mL) | Screening and pre-dose Day -1 up to Day 125. |
Treatment emergent adverse events (TEAEs) were collected from Day 1 up to Day 125 (End of Study).
TEAEs are reported for the Safety population which consisted of all subjects who received at least one dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA19.0 | Systematic Assessment |
The validity of the analytical methods for vanadium determination in human whole blood and urine was not demonstrated. Therefore, no result for vanadium concentration in the clinical samples is reported.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Ipsen Pharma SAS | +33 (0)158335000 | clinical.trials@ipsen.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 7, 2016 | Jun 6, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 20, 2017 | Jun 6, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C033214 | Smectite |
| C016752 | smecta |
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The study is interventional Phase 1 without individual benefit.
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| Screening and pre-dose Day -1 up to Day 125. |
| 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). | Screening and pre-dose Day -1 up to Day 125. |
| 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). | Screening and pre-dose Day -1 up to Day 125. |
| 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). | Screening and pre-dose Day -1 up to Day 125. |
| 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). | Screening and pre-dose Day -1 up to Day 125. |
| 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). | Screening and pre-dose Day -1 up to Day 125. |
| 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). | Screening and pre-dose Day -1 up to Day 125. |
| Mean Change From Baseline in Urine Lead Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | Screening and pre-dose Day -1 up to Day 95. |
| 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. | Screening and pre-dose Day -1 up to Day 95. |
| Mean Change From Baseline in Urine Arsenic Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | Screening and pre-dose Day -1 up to Day 95. |
| Mean Change From Baseline in Urine Barium Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | Screening and pre-dose Day -1 up to Day 95. |
| Mean Change From Baseline in Urine Cadmium Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | Screening and pre-dose Day -1 up to Day 95. |
| Mean Change From Baseline in Urine Cobalt Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | Screening and pre-dose Day -1 up to Day 95. |
| Mean Change From Baseline in Urine Mercury Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | Screening and pre-dose Day -1 up to Day 95. |
| Mean Change From Baseline in Urine Nickel Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | Screening and pre-dose Day -1 up to Day 95. |
| Manchester |
| M13 9NQ |
| United Kingdom |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | 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. |
|
|
| 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). | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 125. |
|
|
|
| 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). | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 125. |
|
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|
| 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). | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 125. |
|
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|
| 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). | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 125. |
|
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| 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). | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 125. |
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| 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). | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 125. |
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| 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). | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 125. |
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| Secondary | Mean Change From Baseline in Urine Lead Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
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| 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
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| Secondary | Mean Change From Baseline in Urine Arsenic Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
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| Secondary | Mean Change From Baseline in Urine Barium Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
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| Secondary | Mean Change From Baseline in Urine Cadmium Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
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|
| Secondary | Mean Change From Baseline in Urine Cobalt Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
|
|
|
| Secondary | Mean Change From Baseline in Urine Mercury Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
|
|
|
| Secondary | Mean Change From Baseline in Urine Nickel Levels During the Treatment Period and Post-treatment Follow-up Period | 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. | 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. | Posted | Mean | 95% Confidence Interval | ng/mL | Screening and pre-dose Day -1 up to Day 95. |
|
|
|
| 0 |
| 35 |
| 0 |
| 35 |
| 30 |
| 35 |
| Dizziness | Nervous system disorders | MedDRA19.0 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA19.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA19.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA19.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA19.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA19.0 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA19.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA19.0 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA19.0 | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA19.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Irritable bowel syndrome | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA19.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA19.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA19.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA19.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA19.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA19.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Onycholasis | Skin and subcutaneous tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Blood glucose increased | Investigations | MedDRA19.0 | Systematic Assessment |
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| Transferrin increased | Investigations | MedDRA19.0 | Systematic Assessment |
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| Blood iron increased | Investigations | MedDRA19.0 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA19.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA19.0 | Systematic Assessment |
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| Chemical injury | Injury, poisoning and procedural complications | MedDRA19.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA19.0 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA19.0 | Systematic Assessment |
|
| Pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA19.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA19.0 | Systematic Assessment |
|
The sponsor shall have the right and title to all documentation, reports, records, data, specimens or other work product generated in connection with the performance of the study. All materials, documents, and information of every kind and description supplied by the sponsor (with the exception of that which is in the public domain), and any sponsor intellectual property shall be the sole and exclusive property of the the sponsor.
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| 3 hours post-dose, Second Dose Day 1 |
|
|
| Pre-dose, Third Dose Day 1 |
|
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| 3 hours post-dose, Third Dose Day 1 |
|
|
| 6 hours post-dose, Third Dose Day 1 |
|
|
| Pre-dose, First Dose Day 2 |
|
|
| Pre-dose, First Dose Day 8 |
|
|
| Pre-dose, First Dose Day 15 |
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|
| Pre-dose, First Dose Day 22 |
|
|
| Pre-dose, First Dose Day 29 |
|
|
| 2 hours post-dose, First Dose Day 35 |
|
|
| Pre-dose, Second Dose Day 35 |
|
|
| 3 hours post-dose, Second Dose Day 35 |
|
|
| Pre-dose, Third Dose Day 35 |
|
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| 3 hours post-dose, Third Dose Day 35 |
|
|
| 6 hours post-dose, Third Dose Day 35 |
|
|
| Day 36 morning |
|
|
| Day 65 (follow-up |
|
|
| Day 95 (follow-up) |
|
|
| Day 125 (End of Study) |
|
|
|
| 3 hours post-dose, Second Dose Day 1 |
|
|
| Pre-dose, Third Dose Day 1 |
|
|
| 3 hours post-dose, Third Dose Day 1 |
|
|
| 6 hours post-dose, Third Dose Day 1 |
|
|
| Pre-dose, First Dose Day 2 |
|
|
| Pre-dose, First Dose Day 8 |
|
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| Pre-dose, First Dose Day 15 |
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| Pre-dose, First Dose Day 22 |
|
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| Pre-dose, First Dose Day 29 |
|
|
| 2 hours post-dose, First Dose Day 35 |
|
|
| Pre-dose, Second Dose Day 35 |
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|
| 3 hours post-dose, Second Dose Day 35 |
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|
| Pre-dose, Third Dose Day 35 |
|
|
| 3 hours post-dose, Third Dose Day 35 |
|
|
| 6 hours post-dose, Third Dose Day 35 |
|
|
| Day 36 morning |
|
|
| Day 65 (follow-up) |
|
|
| Day 95 (follow-up) |
|
|
| Day 125 (End of Study) |
|
|
|
| 3 hours post-dose, Second Dose Day 1 |
|
|
| Pre-dose, Third Dose Day 1 |
|
|
| 3 hours post-dose, Third Dose Day 1 |
|
|
| 6 hours post-dose, Third Dose Day 1 |
|
|
| Pre-dose, First Dose Day 2 |
|
|
| Pre-dose, First Dose Day 8 |
|
|
| Pre-dose, First Dose Day 15 |
|
|
| Pre-dose, First Dose Day 22 |
|
|
| Pre-dose, First Dose Day 29 |
|
|
| 2 hours post-dose, First Dose Day 35 |
|
|
| Pre-dose, Second Dose Day 35 |
|
|
| 3 hours post-dose, Second Dose Day 35 |
|
|
| Pre-dose, Third Dose Day 35 |
|
|
| 3 hours post-dose, Third Dose Day 35 |
|
|
| 6 hours post-dose, Third Dose Day 35 |
|
|
| Day 36 morning |
|
|
| Day 65 (follow-up) |
|
|
| Day 95 (follow-up) |
|
|
| Day 125 (End of Study) |
|
|
|
| 3 hours post-dose, Second Dose Day 1 |
|
|
| Pre-dose, Third Dose Day 1 |
|
|
| 3 hours post-dose, Third Dose Day 1 |
|
|
| 6 hours post-dose, Third Dose Day 1 |
|
|
| Pre-dose, First Dose Day 2 |
|
|
| Pre-dose, First Dose Day 8 |
|
|
| Pre-dose, First Dose Day 15 |
|
|
| Pre-dose, First Dose Day 22 |
|
|
| Pre-dose, First Dose Day 29 |
|
|
| 2 hours post-dose, First Dose Day 35 |
|
|
| Pre-dose, Second Dose Day 35 |
|
|
| 3 hours post-dose, Second Dose Day 35 |
|
|
| Pre-dose, Third Dose Day 35 |
|
|
| 3 hours post-dose, Third Dose Day 35 |
|
|
| 6 hours post-dose, Third Dose Day 35 |
|
|
| Day 36 morning |
|
|
| Day 65 (follow-up) |
|
|
| Day 95 (follow-up) |
|
|
| Day 125 (End of Study) |
|
|
|
| 3 hours post-dose, Second Dose Day 1 |
|
|
| Pre-dose, Third Dose Day 1 |
|
|
| 3 hours post-dose, Third Dose Day 1 |
|
|
| 6 hours post-dose, Third Dose Day 1 |
|
|
| Pre-dose, First Dose Day 2 |
|
|
| Pre-dose, First Dose Day 8 |
|
|
| Pre-dose, First Dose Day 15 |
|
|
| Pre-dose, First Dose Day 22 |
|
|
| Pre-dose, First Dose Day 29 |
|
|
| 2 hours post-dose, First Dose Day 35 |
|
|
| Pre-dose, Second Dose Day 35 |
|
|
| 3 hours post-dose, Second Dose Day 35 |
|
|
| Pre-dose, Third Dose Day 35 |
|
|
| 3 hours post-dose, Third Dose Day 35 |
|
|
| 6 hours post-dose, Third Dose Day 35 |
|
|
| Day 36 morning |
|
|
| Day 65 (follow-up) |
|
|
| Day 95 (follow-up) |
|
|
| Day 125 (End of Study) |
|
|
|
| 3 hours post-dose, Second Dose Day 1 |
|
|
| Pre-dose, Third Dose Day 1 |
|
|
| 3 hours post-dose, Third Dose Day 1 |
|
|
| 6 hours post-dose, Third Dose Day 1 |
|
|
| Pre-dose, First Dose Day 2 |
|
|
| Pre-dose, First Dose Day 8 |
|
|
| Pre-dose, First Dose Day 15 |
|
|
| Pre-dose, First Dose Day 22 |
|
|
| Pre-dose, First Dose Day 29 |
|
|
| 2 hours post-dose, First Dose Day 35 |
|
|
| Pre-dose, Second Dose Day 35 |
|
|
| 3 hours post-dose, Second Dose Day 35 |
|
|
| Pre-dose, Third Dose Day 35 |
|
|
| 3 hours post-dose, Third Dose Day 35 |
|
|
| 6 hours post-dose, Third Dose Day 35 |
|
|
| Day 36 morning |
|
|
| Day 65 (follow-up) |
|
|
| Day 95 (follow-up) |
|
|
| Day 125 (End of Study) |
|
|
|
| 3 hours post-dose, Second Dose Day 1 |
|
|
| Pre-dose, Third Dose Day 1 |
|
|
| 3 hours post-dose, Third Dose Day 1 |
|
|
| 6 hours post-dose, Third Dose Day 1 |
|
|
| Pre-dose, First Dose Day 2 |
|
|
| Pre-dose, First Dose Day 8 |
|
|
| Pre-dose, First Dose Day 15 |
|
|
| Pre-dose, First Dose Day 22 |
|
|
| Pre-dose, First Dose Day 29 |
|
|
| 2 hours post-dose, First Dose Day 35 |
|
|
| Pre-dose, Second Dose Day 35 |
|
|
| 3 hours post-dose, Second Dose Day 35 |
|
|
| Pre-dose, Third Dose Day 35 |
|
|
| 3 hours post-dose, Third Dose Day 35 |
|
|
| 6 hours post-dose, Third Dose Day 35 |
|
|
| Day 36 morning |
|
|
| Day 65 (follow-up) |
|
|
| Day 95 (follow-up) |
|
|
| Day 125 (End of Study) |
|
|
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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