Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00006455

Trial Description

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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

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00006455
  •   2015/04/30
  •   2013/12/09
  •   no
  •   [---]*
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Secondary IDs

  •   NCT02009878  (ClinicalTrials.gov)
  •   156-12-203  (Otsuka Pharmaceutical Development & Commercialization, Inc.)
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Health Condition or Problem studied

  •   Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
  •   E22.2 -  Syndrome of inappropriate secretion of antidiuretic hormone
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Interventions/Observational Groups

  •   Drug: tolvaptan
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, caregiver, investigator/therapist
  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   I-II
  •   [---]*
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Primary Outcome

- Pharmacodynamics: Maximal change from baseline and time of maximal change from baseline in serum sodium concentration following tolvaptan administration.; time frame: 2 days

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Secondary Outcome

- 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
- 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
- 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
- 0 to 6, 0 to 12, and 0 to 24 hour urine output from baseline (corresponding intervals on Day 0).; time frame: 2 days

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Countries of Recruitment

  •   Czech Republic
  •   Denmark
  •   Germany
  •   Hungary
  •   Spain
  •   Sweden
  •   United Kingdom
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Locations of Recruitment

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Recruitment

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  •   2013/11/30
  •   30
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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.

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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.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Otsuka Pharmaceutical Development & Commercialization, Inc.
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    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
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  • start of 1:1-Block address scientific-contact
    • Susanne Baumann 
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    • Susanne Baumann 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/07/16
* This entry means the parameter is not applicable or has not been set.