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Trial record 1 of 1 for:    NCT03934307
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A Study to Evaluate ALN-AGT01 in Patients With Hypertension

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ClinicalTrials.gov Identifier: NCT03934307
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) effects of subcutaneous (SC) ALN-AGT01 in participants with hypertension. The study will be conducted in 4 parts: Part A will be a single ascending dose (SAD) phase in hypertensive participants, Part B will be a single dose (SD) phase in hypertensive participants with controlled salt intake, Part C will be a multiple dose (MD) phase in hypertensive participants, and Part D will be a MD phase in hypertensive participants who are obese.

Condition or disease Intervention/treatment Phase
Hypertension Drug: ALN-AGT01 Drug: ALN-AGT01-Matching Placebo Drug: Irbesartan Drug: Irbesartan-Matching Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Dose and Active Comparator-Controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-AGT01 in Patients With Hypertension
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Irbesartan

Arm Intervention/treatment
Experimental: Part A: SAD: ALN-AGT01
Participants will be administered a single dose of ALN-AGT01.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.

Placebo Comparator: Part A: SAD: ALN-AGT01-Matching Placebo
Participants will be administered a single dose of ALN-AGT01-matching placebo.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.

Experimental: Part B: SD: ALN-AGT01
Participants with controlled salt intake will be administered a single dose of ALN-AGT01.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.

Placebo Comparator: Part B: SD: ALN-AGT01-Matching Placebo
Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.

Experimental: Part C: MD: ALN-AGT01 + Irbesartan-Matching Placebo
Participants will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.

Drug: Irbesartan-Matching Placebo
Irbesartan-matching placebo will be administered orally.

Active Comparator: Part C: MD: ALN-AGT01-Matching Placebo + Irbesartan
Participants will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.

Drug: Irbesartan
Irbesartan will be administered orally.

Experimental: Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo
Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.

Drug: Irbesartan-Matching Placebo
Irbesartan-matching placebo will be administered orally.

Active Comparator: Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan
Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.

Drug: Irbesartan
Irbesartan will be administered orally.




Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) [ Time Frame: Parts A and B: each up to approximately 12 months; Parts C and D: each up to approximately 18 months ]

Secondary Outcome Measures :
  1. Change from Baseline in Blood Angiotensinogen (AGT) Level [ Time Frame: Parts A and B: each up to approximately 12 months; Parts C and D: each up to approximately 18 months ]
  2. Maximum Observed Plasma Concentration (Cmax) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Up to day 15; Parts C and D: Up to day 99 ]
  3. Time to Maximum Observed Plasma Concentration (tmax) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Up to day 15; Parts C and D: Up to day 99 ]
  4. Elimination Half-life (t1/2beta) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Up to day 15; Parts C and D: Up to day 99 ]
  5. Area Under the Concentration-time Curve (AUC) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Up to day15; Parts C and D: Up to day 99 ]
  6. Apparent Clearance (CL/F) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Up to day 15; Parts C and D: Up to day 99 ]
  7. Apparent Volume of Distribution (V/F) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Up to day 15; Parts C and D: Up to day 99 ]
  8. Fraction Excreted in Urine (fe) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Days 1 and 2; Parts C and D: Up to day 86 ]
  9. Renal Clearance (CLR) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A and B: Days 1 and 2; Parts C and D: Up to day 86 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has mild to moderate hypertension with mean sitting systolic blood pressure (SBP) of >130 and ≤159 mmHg without hypertensive medication
  • Parts A, B, and C: Has body mass index (BMI) ≥18 and ≤35 kg/m^2
  • Part D: Has BMI >30 and ≤50 kg/m^2
  • Has a normal 12-lead electrocardiogram (ECG)
  • Is a nonsmoker

Exclusion Criteria:

  • Has secondary hypertension
  • Has orthostatic hypotension
  • Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2
  • Recently received an investigational agent
  • Has diabetes mellitus
  • Has history of any cardiovascular event
  • Has history of intolerance to SC injection(s)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03934307


Contacts
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Contact: Alnylam Clinical Trial Information Line 1-877-ALNYLAM clinicaltrials@alnylam.com
Contact: Alnylam Clinical Trial Information Line 1-877-256-9526 clinicaltrials@alnylam.com

Locations
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United Kingdom
Clinical Trial Site Recruiting
Belfast, United Kingdom
Clinical Trial Site Recruiting
London, United Kingdom
Clinical Trial Site Recruiting
Manchester, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Stephen Huang, MD Alnylam Pharmaceuticals

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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03934307     History of Changes
Other Study ID Numbers: ALN-AGT01-001
2019-000129-39 ( EudraCT Number )
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Irbesartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action