Clinical trial NCT03795389: Study to Assess PK, Safety and Tolerability in Patients With DM and CKD
Official title: A Multi-Center Open-label Investigation to Assess the Pharmacokinetics, Safety and Tolerability of DM199 in Patients With Diabetes Mellitus and Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Kidney Disease
Chronic Kidney Disease, Stage 3 (Moderate)
Chronic Kidney Disease, Stage 4 (Severe)
Diabetes
Keywords: Diabetes
Chronic Kidney Disease
Lead sponsor: DiaMedica Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2019-01-07
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An open-label, phase IB, multi-center study evaluating DM199 in subjects with Type 1 Diabetes or Type 2 Diabetes and Stage 3 or 4 Chronic Kidney Disease. The primary objectives of this study are to evaluate safety, tolerability, and PK profile of DM199 in these subjects.

Detailed description: The study evaluates the safety, tolerability, and PK profile of DM199 in subjects with T1D or T2D and with Stage 3 or Stage 4 CKD. Additionally, this study evaluates urine concentrations of KLK1 pre and post dose.

Cohort 1: Subjects with T1D or T2D and Stage 3 CKD will be administered one of three DM199 doses: 3.0 ug/kg or 5.0 ug/kg or 8.0 ug/kg single SC dose. Cohort 2: Subjects with T1D or T2D and Stage 4 CKD will be administered a single 3.0 µg/kg single SC dose. Secondary and exploratory study objectives include collection and analysis of vital signs, biomarkers, eGFR, blood glucose, and ECG's.

Eligibility criteria: Inclusion Criteria:

* Subject is willing and able to provide informed consent for study participation.
* Subject is ≥ 18 years of age.
* Subject has an established diagnosis of T1D or T2D as determined by medical evaluation at screen.
* Subjects A1c \<9.8%
* Subject is clinically stable with respect to underlying renal impairment and diabetes, as assessed by the Investigator's medical evaluation.
* Subject has been diagnosed with Stage 3 CKD as defined by eGFR (MDRD) between 30 - \<60 or Stage 4 as defined by eGFR \<30 (not on dialysis) at screening.
* Subject has a body mass index (BMI) between 18 to 45 kg/m2 (inclusive).

Exclusion Criteria:

* Subject has positive drug test for drugs of abuse and/or positive alcohol breath test at screening and Day 0.
* Subject is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits.
* Subject has a history of significant allergic diathesis such as urticaria, angioedema, or anaphylaxis.
* Subject has had any live vaccination ≤ 3 months prior to enrollment or will require vaccination during the study.
* Subject must not be taking an ACEi medication for 5 half-lives prior to study drug administration and for 5 days post study drug administration.
* Subject is unwilling or unable to limit smoking to ≤ 10 cigarettes per day (or other products that contain nicotine limited to \< 200 mg of nicotine/day) during the study participation period.
* Subject has a current malignancy or active malignancy ≤ 3 years prior to enrollment except basal cell or squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy and ≥ six months have elapsed since the procedure.
* Subject has an active infection at the time of enrollment, and/or a history of clinically significant acute bacterial, viral, or fungal systemic infections that required systemic treatment in the last four weeks prior to enrollment.
* Subject has known medical history of alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).
* Subject has serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (Anti-HCV) at screen.
* Subject is pregnant or nursing or is planning a pregnancy during the study period.
* Subject is male or female of childbearing potential, is participating in sexual activity that could lead to pregnancy and is unable or unwilling to practice medically effective contraception during the study.
* Subject has received any investigational drug or device within 14 days (or 5 half lives, whichever is longer) prior to study drug administration on Day 1
* Subject has renal artery stenosis as determine at screen with medical history.
* Subject has hypotension as defined by systolic blood pressure ≤ 90 and diastolic blood pressure ≤ 60 mmHg.
* Subject has Proteinuria: PCR\>2000mg/gm (spot testing).
* Subject does not have adequate venous access for blood sampling.
* Subject has any other medical condition which, in the opinion of the Investigator, will make participation medically unsafe or interfere with the study results.
* Subject has any other clinically significant abnormalities in laboratory test results at screening that would, in the opinion of the Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data.
* Subject has any of the following conditions as determined by ECG or medical record:

  * Any significant arrhythmia or conduction abnormality, which, in the opinion of the Investigators and Medical Monitor, may interfere with the safety of the subject.
* Subject is taking Cimetidine, St. John's Wort, or any other herbal or probiotic supplement.

Primary outcomes:
measure: Safety as assessed by incidence, severity, and causality of adverse events
timeFrame: 11 days
measure: Tolerability as assessed by incidence and severity of AEs
timeFrame: 11 days
measure: plasma measurements of DM199
timeFrame: 11 days
measure: DM199 urine concentrations of KLK1
timeFrame: 11 days
Secondary outcomes:
measure: C Reactive protein (CRP)
timeFrame: 11 days
measure: Matrix Metalloproteinase-9 (MMP-9)
timeFrame: 11 days
measure: Vascular Endothelial Growth Factor (VEGF)
timeFrame: 11 days
measure: Nitric Oxide (NO)
timeFrame: 11 days
measure: Serum creatinine
timeFrame: 11 days
measure: Cystatin C
timeFrame: 11 days
measure: neutrophil gelatinase-associated prostaglandin E2
timeFrame: 11 days
measure: Urine Kidney Injury Molecule-1 (Kim1)
timeFrame: 11 days
Other outcomes:
measure: serum creatinine
timeFrame: 11 days
measure: Blood glucose
timeFrame: 11 days
Locations:
city: Hialeah
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center Inc
state: Florida
city: Saint Paul
country: United States
facility: Prism Research
state: Minnesota
Study officials:
affiliation: DiaMedica Inc.
name: Harry Alcorn, Pharm.D.
role: STUDY_DIRECTOR
References: