Clinical Trials Register

Summary
EudraCT Number:	2021-005865-42
Sponsor's Protocol Code Number:	PEChoPro
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-03-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2021-005865-42

A.3

Full title of the trial

Does Cholestyramine/Colesevelam and Probenecid increase the elimination of Perfluoroalkyl substances? An experimental study of highly exposed individuals in Ronneby, Sweden.

Ökar Kolestyramin/Kolesevelam och Probenecid eliminationen av Perfluoroalkylsubstanser? En experimentell studie av högexponerade individer i Ronneby.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Does Cholestyramine/Colesevelam and Probenecid increase the excretion of Perfluoroalkyl substances? An study of individuals with high levels of Perfluoroalkyl substances in Ronneby, Sweden.

Ökar Kolestyramin/Kolesevelam och Probenecid utsöndringen av Perfluoroalkylsubstanser? En studie av individer med höga nivåer av Perflouroalkylsubstanser i Ronneby.

A.4.1

Sponsor's protocol code number

PEChoPro

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Gothenburg
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Swedish Research Council (VR)
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Of Gothenburg
B.5.2	Functional name of contact point	Axel Andersson
B.5.3	Address:
B.5.3.1	Street Address	Medicinaregatan 16a
B.5.3.2	Town/ city	Gothenburg
B.5.3.3	Post code	405 30
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+4631786 68 40
B.5.6	E-mail	axel.andersson.2@gu.se

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Kolestyramin
D.3.4	Pharmaceutical form	Powder for oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLESTYRAMINE ANHYDROUS
D.3.9.2	Current sponsor code	Cholestyramine
D.3.9.4	EV Substance Code	SUB127291
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Probenecid
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PROBENECID
D.3.9.1	CAS number	57-66-9
D.3.9.4	EV Substance Code	SUB10053MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Kolesevelam
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Colesevelam
D.3.9.1	CAS number	182815-43-6
D.3.9.2	Current sponsor code	Cholestagel
D.3.9.4	EV Substance Code	SUB01423MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	625
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

An intervention trial on healthy subjects to study the importance of enterohepatic recirculation and renal organic anion transporters on elimination of Perfluoroalkyl substances (PFAS). The intervention will consist of two different medications - Cholestyramine/colesevelam and Probenecid. The effects will be evaluated in healthy subjects with high PFAS-levels.

En interventionsstudie på friska individer för att studera vikten av enterohepatisk recirkulation och organiska anjonstransportörer i njuren på eliminationen av Perfluoroalkylsubstanser (PFAS). Interventionen kommer bestå i två olika behandlingar - Kolestyramin/Kolesevelam och Probenecid. Effekterna kommer att utvärderas i friska individer med höga PFAS-nivåer.

E.1.1.1

Medical condition in easily understood language

An trial on healthy subjects to study the excretion of Perfluoroalkyl substances by giving cholesterol lowering medicine Cholestyramine/Colesevelam or gout-treating medicine Probenecid.

En studie på friska individer för att studera utsöndringen av Perfluoroalkylsubstanser genom att ge kolesterolsänkande läkemedlet Kolestyramin/kolesevelam och gikt-behandlande läkemedlet Probenecid.

E.1.1.2

Therapeutic area

Body processes [G] - Chemical Phenomena [G02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10050654
E.1.2	Term	Toxicology NOS
E.1.2	System Organ Class	10022891 - Investigations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10063599
E.1.2	Term	Exposure to chemical pollution
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The general aim is to study the importance of enterohepatic recirculation and renal organic anion transporters on elimination of Perfluoroalkyl substances (PFAS).

In order to study this aim, this study is divided into two parts – a proof-of-concept, shorter trial; and a longer follow-up trial.

Specific research questions for part 1 (proof-of-concept):
• Does a one-week Cholestyramine treatment lead to an increased elimination of PFAS in faeces?
• Does a one-week Probenecid treatment lead to an increased elimination of PFAS in urine?

Depending on the results in part 1, the following specific research questions can be applicable for part 2:
• Does a twelve weeks Colesevelam treatment lead to an increased elimination rate of PFAS?
• Is there an additive or synergistic effect of combined twelve-week Colesevelam and Probenecid treatment? What is the maximum effect?

Det vetenskaplig syftet är att undersöka betydelsen av enterohepatiska återupptaget och Organiska Anjonstransportörer i njuren på eliminationen av Perfluoroalkylsubstnaser.

För att studera detta syfte så delas studien in i två delar - en proof-of-concept, kortare del; och en längre uppföljningsdel.

Specifika frågeställningar för del 1 (proof-of-concept):
• Leder en veckas behandling med Kolestyramin till en ökad utsöndring av PFAS i avföring?
• Leder en veckas behandling med Probenecid till en ökad utsöndring av PFAS i urinen?

Beroende på resultaten i del 1 så kan följande frågeställningar bli aktuella för del 2:
• Leder en tolvveckorsbehandling med Kolesevelam till en ökad utsöndring av PFAS?
• Finns det en additiv eller synergistisk effekt av kombinerad tolvveckorsbehandling med Kolesevalm och Probenecid? Vad är den maximala effekten?

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Men and women aged 20-45
• Previous participation in Ronneby Biomarker cohort, established 2014-15.
• Given informed, written consent

* Män och kvinnor 20-45 år
* Tidigare deltagande i Ronneby Biomarkörskohort, grundad 2014-15
* Givet informerat, skriftligt samtycke

E.4

Principal exclusion criteria

• Contraindications towards the study medications
• Medication that interacts with the study medications
• Previous or current kidney, liver or inflammatory bowel disease
• Chronic, systemic disease
• Known or suspected allergy against any of the medications
• Pregnant or lactating women, or women who plan to be pregnant during the trial
• Treatment or disease that according to the investigator might affect the treatment or the study results
• Intellectual disability, reluctance or language barriers that entail difficulties in understanding participation in the study.
• Participation in another clinical, intervention study (except for our vaccine study)

* Kontraindikationer mot studieläkemedlen
* Läkemedelsbruk som interagerar med studieläkemedel
* Tidigare eller nuvarande njur-, lever- eller inflammatorisk tarmsjukdom
* Kronisk systemsjukdom
* Känd eller misstänkt allergi mot någon av läkemedlen
* Graviditet, amning eller planer på att bli gravid inom studietiden
* Behandling eller sjukdom som enligt prövaren kan påverka behandlingen eller studieresultatet
* Intellektuell funktionsnedsättning, ovilja eller språkbarriärer som medger svårigheter att förstå deltagande i studien
* Deltagande i en annan klinisk interventionsstudie, dock inte vår vaccinationsstudie (PIRVACoV)

E.5 End points

E.5.1

Primary end point(s)

Part 1: Change of PFAS in faeces and in urine during the treatment period.

Part 2: Change of PFAS in serum during the treatment period.

Del 1: Förändring av PFAS i avföring och i urin under studieperioden.

Del 2: Förändring av PFAS i serum under studieperioden.

E.5.1.1

Timepoint(s) of evaluation of this end point

Before, during and after each treatment period.

Part 1: 1 week with each treatment, with cross-over design so that every participant gets each treatment and being control.

Part 2: 12 week with each treatment, with cross-over design so that every participant gets each treatment and being control.

Före, under och efter varje behandlingsperiod.

Del 1: 1 vecka med varje behandling, med överkorsningsdesign så att varje deltagare får varje behandling och får vara sin egen kontroll.

Del 2: 12 veckor med varje behandling, med överkorsningsdesign så att varje deltagare får varje behandling och får vara sin egen kontroll.

E.5.2

Secondary end point(s)

Not applicable.

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Toxicokinetic, to understand the elimination mechanisms for Perfluoroalkyl substances

Toxikokinetisk, att förstå eliminationsmekanismerna för Perfluoroalkylsubstanser.

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Ingen behandling.

No treatment.

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

När sista deltagaren lämnar sitt sista prov.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2022-03-24.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

Inga.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-05-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-08-01

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