Trial record 8 of 32 for:    "Diabetes Insipidus" [DISEASE]

A PK Study of 3 Dosages of Tolvaptan in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT02009878
First received: December 9, 2013
Last updated: September 26, 2014
Last verified: September 2014
  Purpose

This is a study to evaluate how the body handles and metabolizes (PK) the various doses of the drug Tolvaptan, and what the effect (PD) of the various doses of Tolvaptan are on the content of "salt" in blood and urine


Condition Intervention Phase
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Drug: tolvaptan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1b, Multicenter, Pilot, Randomized, Double-blind Trial to Determine the Pharmacokinetics and Pharmacodynamics of Orally Administered Tolvaptan 3.75, 7.5, and 15 mg Tablets in Subjects With Syndrome of Inappropriate Antidiuretic Hormone Secretion

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Pharmacodynamics: Maximal change from baseline and time of maximal change from baseline in serum sodium concentration following tolvaptan administration. [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PK: The secondary PK endpoints for this trial are: Cmax, time to maximum (peak) plasma concentration (tmax), and AUC(infinity) for tolvaptan in plasma. [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  • PD: The secondary PD endpoints for this trial are: Sodium serum concentrations and change from baseline (time 0 of each day) by timepoint; [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  • 0 to 6, 0 to 12, and 0 to 24 hour fluid intake and fluid balance (intake-urine output) and change from baseline (corresponding intervals on Day 0); [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  • 0 to 6, 0 to 12, and 0 to 24 hour urine output from baseline (corresponding intervals on Day 0). [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: November 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
tolvaptan 3.75 mg
tolvaptan 3.75 mg
Drug: tolvaptan
Subjects will receive a single dose of 3.75, 7.5 or 15 mg of tolvaptan on study Day 1
Other Name: SAMSCA
tolvaptan 7.5 mg
tolvaptan 7.5 mg
Drug: tolvaptan
Subjects will receive a single dose of 3.75, 7.5 or 15 mg of tolvaptan on study Day 1
Other Name: SAMSCA
tolvaptan 15 mg
tolvaptan 15 mg
Drug: tolvaptan
Subjects will receive a single dose of 3.75, 7.5 or 15 mg of tolvaptan on study Day 1
Other Name: SAMSCA

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects greater than or equal to 18 years of age or the age of legal consent.
  • Must have a BMI less than or equal to 32.0 kg/m2.
  • Subjects must have a diagnosis of SIADH prior to randomization.
  • Persistent euvolemic hyponatremia, evidenced by 3 serum sodium assessments of between 120 and 133 mmol/L, inclusive drawn locally as follows: one during the screening period, a second at check-in on Day -1, a third on Day 0 (12-24 hours prior to dosing), which will serve as the baseline value for efficacy endpoints
  • Subjects with relatively intact renal function, ie, estimated glomerular filtration rate using the CKD-EPI formula of greater than or equal to 60 mL/min/1.73m2.
  • Ability to provide written, informed consent prior to initiation of any trial related procedures, and ability, in the opinion of the PI, to comply with all the requirements of the trial.
  • Sexually active males who are practicing a highly effective method of birth control during the trial and for 30 days after the last dose of trial medication or who will remain abstinent during the trial and for 30 days after the last dose, or sexually active females of childbearing potential who are practicing a highly effective method of birth control during the trial and for 30 days after the last dose of trial medication or who will remain abstinent during the trial and for 30 days after the last dose, or female subjects of nonchildbearing potential (surgically sterile or postmenopausal [1 year post menses]). If employing birth control, 1 of the following highly effective methods (failure rate <1%) must be used: vasectomy, tubal ligation, intrauterine device containing hormone (Mirena), combined oral contraceptive, hormone implants or hormone injections.

Exclusion Criteria:

  • Daily use of diuretics within 14 days prior to screening assessments or randomization or the requirement for constant diuretic use for any reason.
  • Clinically assessed hypovolemic state.
  • Inability to respond to thirst.
  • Subjects who cannot perceive thirst.
  • Subjects with anuria.
  • Urgent need to raise serum sodium acutely.
  • Urinary outflow obstruction unless the subject is, or can be, catheterized during the trial.
  • Severe hepatic impairment. Child-Pugh Class C (score of 10 or greater).
  • Subjects who receive any medication given for the purpose of raising serum sodium while undergoing qualifying serum sodium assessments. Specifically: Hypertonic saline (including normal saline challenge) within 8 hours before each qualifying serum sodium screening assessment; Urea, lithium, demeclocycline, conivaptan, or tolvaptan within 4 days of each qualifying serum sodium screening assessment; Loop diuretics (eg. furosemide, bumetanide, torsemide) within 48 hours of each qualifying serum sodium screening assessment; Other treatment (including normal saline or oral sodium containing supplements) for the purpose of increasing serum sodium within 24 hours of each qualifying serum sodium screening assessment. Final determination will be made in consultation with the sponsor.
  • Subjects with medication induced SIADH who have not been on stable medication for 3 months.
  • CYP3A4 inhibitors taken within 5 elimination half-lives or within 96 hours of dosing, which ever time is longer. Final determination will be made in consultation with the sponsor.
  • CYP3A4 inducers taken within 72 hours after 5 elimination half-lives (eg, rifampin, St. Johns Wort).
  • Chemotherapy agents given in the previous 7 days prior to dosing or within 5 elimination half-lives of the agent; whichever is longer.
  • Clinically significant abnormality in past medical history, or at the Screening physical examination, that in the investigator's or sponsor's opinion may place the subject at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. This includes, but is not limited to, history of or concurrent cardiac, hepatic, renal, neurologic, endocrine, GI, respiratory, hematologic, and immunologic disease.
  • History of drug and/or alcohol abuse within 6 months prior to Screening.
  • History of or current hepatitis or acquired immunodeficiency syndrome or carriers of HBsAg, anti-HCV, and/or HIV antibodies.
  • History of any significant drug allergy.
  • A positive alcohol test and/or drug screen for substance of abuse at Screening or upon Check-in to the clinical site.
  • Subjects having taken an investigational drug within 30 days preceding trial entry.
  • Any history of significant bleeding or hemorrhagic tendencies.
  • A history of difficulty in donating blood.
  • The donation of blood or plasma within 30 days prior to dosing.
  • Consumption of alcohol and/or food and beverages containing methylxanthines, pomelo fruit, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours prior to dosing.
  • Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to Screening (eg, occupational exposure to pesticides, organic solvents).
  • Has Screening liver function values > 3 x ULN.
  • Has primary polydipsia.
  • Inability to take oral medications.
  • Subjects who have supine blood pressure, after resting for greater than or equal to 3 minutes, higher than 140/90 mmHg or lower than 100/50 mmHg. The sponsor may allow exceptions if they are not deemed clinically significant.
  • Subjects who have a supine pulse rate, after resting for greater than or equal to 3 minutes, outside the range of 40 to 90 bpm. The sponsor may allow exceptions significant.
  • History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial.
  • Any subject who, in the opinion of the investigator, should not participate in the trial.
  • Subjects who are pregnant or breastfeeding. A negative serum pregnancy test must be confirmed prior to randomization for all female subjects of childbearing potential.
  • Subjects with Type 1 diabetes.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02009878

Contacts
Contact: Susanne Baumann 0041 61 270 81 42 susanne.baumann@quintiles.com

Locations
Czech Republic
Vseobecna fakultni nemocnice V Praze Recruiting
Praha, Czech Republic, 128 08
Principal Investigator: Jan Jiskra, Dr.         
Denmark
Holstebro Regionhospital Recruiting
Holstebro, Denmark, 7500
Principal Investigator: Erling Pedersen, Dr         
Germany
Medizinische Klinik im Klinikum Hannover Recruiting
Hannover, Niedersachsen, Germany, 30167
Principal Investigator: Johannes Hensen, Prof         
Universitätsklinikum C.-G.-Carus Recruiting
Dresden, Sachsen, Germany, 01307
Principal Investigator: Martin Wermke, Dr. med         
Evangelische Lungenklinik Berlin Recruiting
Berlin, Germany, 13125
Principal Investigator: Christian Grohé, Prof.         
Universitaetsklinikum Koeln Recruiting
Koeln, Germany, 50937
Principal Investigator: Volker Burst, Dr.         
Universitaetsklinikum Schleswig-Holstein - Campus Luebeck Recruiting
Luebeck, Germany, 23538
Principal Investigator: Christian Haas, Prof.         
Hungary
Semmelweis Egyetem AOK Recruiting
Budapest, Hungary, 1083
Principal Investigator: Istvan Takacs, Dr         
Spain
Hospital Clinic i Provincial de Barcelona Active, not recruiting
Barcelona, Spain, 08036
Hospital Universitario Clinico San Carlos Recruiting
Madrid, Spain, 28040
Principal Investigator: Isabelle Runkle de la Vega, Dr.         
Sweden
Sahlgrenska Universitetssjukhuset Recruiting
Göteborg, Sweden, 41345
Principal Investigator: Gudmundur Johannsson, Dr.         
United Kingdom
Birmingham Heartlands Hospital Recruiting
Birmingham, United Kingdom, B9 5SS
Principal Investigator: Jayadave Shakher, Dr.         
Royal Free Hospital Recruiting
London, United Kingdom, NW3 2QG
Principal Investigator: Pierre Bouloux, Prof         
The Christie Hospital Active, not recruiting
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02009878     History of Changes
Other Study ID Numbers: 156-12-203
Study First Received: December 9, 2013
Last Updated: September 26, 2014
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Denmark: Danish Health and Medicines Authority
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Spain: Ministerio de Sanidad, Servicios Sociales e Igualdad
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
SIADH

Additional relevant MeSH terms:
Diabetes Insipidus
Syndrome
Inappropriate ADH Syndrome
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Pituitary Diseases
Endocrine System Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Water-Electrolyte Imbalance
Metabolic Diseases
Vasopressins
Arginine Vasopressin
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasoconstrictor Agents
Cardiovascular Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014