PK Study of IV and Oral Amisulpride in Subjects With Severe Renal Impairment

NCT ID: NCT04849650

Last Updated: 2021-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-03

Study Completion Date

2021-10-30

Brief Summary

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The aim of the study is to understand how Amisulpride is taken up and distributed around the body and how quickly it is eliminated, when given by mouth and into a vein in adults with severe kidney disease. In addition it is important to understand how well tolerated Amisulpride is in this patient population. Healthy adults will be studied to provide a comparison.

Detailed Description

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This will be an open-label, non-randomised, pharmacokinetic study in

* 6 adult subjects with severe renal impairment and end-stage renal disease (i.e., eGFR \< 30 mL/min/1.73 m2) without dialysis.
* 6 matched healthy subjects (control group).

Each subject will be given a single dose of 10 mg IV Amisulpride, followed by a single dose of 10 mg oral Amisulpride given 24 hours later.

Subjects will be admitted to the clinic on Day -1. Dosing will start the following day (Day 1). Serial blood samples will be taken during Days 1-3 to assess the pharmacokinetics of Amisulpride. Subjects will remain in clinic over the duration of the study and will be discharged when the final blood sample is drawn on Day 3.

The tolerability /safety of Amisulpride will be assessed by clinical chemistry and haematology assessments, vital signs, electrocardiograms (ECG), physical examination and adverse event reporting.

Conditions

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Renal Disease, End Stage

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

One group of subjects with renal impairment will receive 10mg IV Amisulpride followed 24 hours later by a 10mg oral dose.

One group of matched healthy subjects will receive 10mg IV Amisulpride followed 24 hours later by a 10mg oral dose.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

All parties will have knowledge of the interventions assigned to each subject.

Study Groups

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Renal Impairment Subjects

10mg dose of IV Amisulpride, followed 24 hours by a 10mg oral dose of Amisulpride

Group Type EXPERIMENTAL

Amisulpride IV

Intervention Type DRUG

A single 10mg IV dose of Amisulpride given over 1 minute

Amisulpride Oral Tablet

Intervention Type DRUG

A single 10mg dose given as an oral tablet

Healthy Subjects

10mg dose of IV Amisulpride, followed 24 hours by a 10mg oral dose of Amisulpride

Group Type EXPERIMENTAL

Amisulpride IV

Intervention Type DRUG

A single 10mg IV dose of Amisulpride given over 1 minute

Amisulpride Oral Tablet

Intervention Type DRUG

A single 10mg dose given as an oral tablet

Interventions

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Amisulpride IV

A single 10mg IV dose of Amisulpride given over 1 minute

Intervention Type DRUG

Amisulpride Oral Tablet

A single 10mg dose given as an oral tablet

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age 18 to 75 years of age at time of signing ICF.
2. Body mass index (BMI) between 18 and 38 kg/m2.
3. Must be willing and able to communicate and participate in the whole study.
4. Must provide written informed consent.
5. Must agree to use an adequate method of contraception
6. Healthy as defined by:

* The absence of clinically significant illness and surgery within 4 weeks prior to dosing. Subjects vomiting within 24 hours pre-dose will be carefully evaluated for upcoming illness/disease. Inclusion pre-dosing is at the discretion of the Principal Investigator;
* The absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic (including cholecystectomy), and metabolic disease;
* The absence of clinically significant history of lactic acidosis and severe hepatomegaly with steatosis;
* The absence of history of suicidal tendency, disposition to seizures, state of confusion, or clinically relevant psychiatric diseases.
7. Normal renal function, i.e., eGFR or creatinine clearance ≥ 90 mL/min/1.73 m2 as calculated using the MDRD4 or Cockcroft-Gault equation; at the Principal Investigator's discretion, 24 hour creatinine clearance may be conducted to determine renal function.
8. Matched to subjects with severe renal impairment for gender, age (± 10 years), and BMI (± 15%) to the extent possible.


1. Age 18 to 75 years of age at time of signing ICF.
2. Body mass index (BMI) between 18 and 38 kg/m2.
3. Must be willing and able to communicate and participate in the whole study.
4. Must provide written informed consent.
5. Must agree to use an adequate method of contraception
6. A diagnosis of renal impairment that has been stable, without significant change in overall disease status in the 3 months prior to screening as determined by the Principal Investigator, with no requirement for dialysis, and an eGFR at screening \< 30 mL/min/1.73 m2 calculated using the MDRD4 equation.

Exclusion Criteria

1. Subjects who have received any IMP in a clinical research study within the 30 days prior to IMP administration on this study.
2. Subjects who are study site, CRO or sponsor employees, or immediate family members of a study site, CRO or sponsor employee.
3. Subjects who have previously been enrolled in this study.
4. Women who are pregnant or breastfeeding.
5. Subjects who have received amisulpride for any indication within the 30 days prior to dosing.
6. Allergy to amisulpride or any of the excipients of amisulpride.
7. History of any drug or alcohol abuse in the 2 years prior to screening.
8. Regular alcohol consumption \>21 units per week in the 6 months prior to screening.
9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
10. History of epilepsy in the 5years prior toscreening.
11. History of clinically significant syncope.
12. Family history of sudden death.
13. Family history of premature cardiovascular death.
14. Clinically significant history or family history of congenital long QT syndrome (e.g.

Romano-Ward syndrome, Jervell and Lange-Nielson syndrome) or Brugada's syndrome.
15. History of clinically significant arrhythmias or ischaemic heart disease (especially ventricular arrhythmias, atrial fibrillation (AF), recent conversion from AF or coronary spasm).
16. Conditions predisposing the volunteer to electrolyte imbalances (e.g. altered nutritional states, chronic vomiting, anorexia nervosa, bulimia nervosa).
17. Clinically significant abnormal biochemistry,haematology or urinalysis at screening as judged by the investigator
18. Positive drugs of abuse test result
19. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results at screening.
20. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening or menses) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the dosing.
21. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 2,000 mg per day acetaminophen) or herbal remedies in the 14 days before IMP administration
22. Administration of a biological product in the context of a clinical research study within 90 days prior to dosing, or concomitant participation in an investigational study involving no drug or device administration.
23. Failure to satisfy the investigator of fitness to participate for any other reason.


1. Subjects who have received any IMP in a clinical research study within the 30 days prior to IMP administration on this study.
2. Subjects who are study site, CRO or sponsor employees, or immediate family members of a study site, CRO or sponsor employee.
3. Subjects who have previously been enrolled in this study.
4. Women who are pregnant or breastfeeding.
5. Subjects who have received amisulpride for any indication within the 30 days prior to dosing.
6. Allergy to amisulpride or any of the excipients of amisulpride.
7. History of any drug or alcohol abuse in the 2 years prior to screening.
8. Regular alcohol consumption \>21 units per week in the 6 months prior to screening.
9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
10. History of epilepsy in the 5years prior to screening.
11. History of clinically significant syncope.
12. Family history of sudden death.
13. Family history of premature cardiovascular death.
14. Clinically significant history or family history of congenital long QT syndrome (e.g.

Romano-Ward syndrome, Jervell and Lange-Nielson syndrome) or Brugada's syndrome.
15. History of clinically significant arrhythmias or unstable ischaemic heart disease (especially ventricular arrhythmias, atrial fibrillation (AF), recent conversion from AF or coronary spasm).
16. Positive drugs of abuse test result, unless caused by a documented prescription drug.
17. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results at screening.
18. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening or menses) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the dosing.
19. Administration of a biological product in the context of a clinical research study within 90 days prior to dosing, or concomitant participation in an investigational study involving no drug or device administration.
20. Failure to satisfy the investigator of fitness to participate for any other reason.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Acacia Pharma Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gabriel Fox, MD

Role: STUDY_DIRECTOR

Chief Medical Officer

Locations

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Panax Clinical Research

Miami Lakes, Florida, United States

Site Status

Countries

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United States

Other Identifiers

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DP10026

Identifier Type: -

Identifier Source: org_study_id