The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants

• Sponsor: Janssen Korea, Ltd., Korea (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01021683
• Collaborator: (none)
• Enrollment: 203
• Duration (Months): 12

Study Details

Study Description

Brief Summary

The purpose of this observational study is to investigate whether a sufficient concentration of itraconazole can influence disappearance of a fever (defeverscence) when intravenous (into the vein) itraconazole is administered for resolving unknown neutropenic fever of participants who are given itraconazole oral solution as a prophylaxis under general treatment conditions.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Neoplasms; Neutropenia; Fever	Drug: Itraconazole

Detailed Description

This is a prospective (study following patients forward in time), open-label (all people know the identity of the intervention), multi-center (conducted in more than one center) observational study to examine the correlation between a sufficient blood concentration of itraconazole and disappearance of a fever (defeverscence) when itraconazole injection is administered for resolving unknown neutropenic fever of participants who are given itraconazole oral solution as a prophylaxis under general treatment conditions. The recommended dose of the drug will be 200 milligram (mg), which will be administered intravenously, twice daily for 2 days (a total of 4 doses) and then 200 mg once daily for 12 days. After the administration for a total of 14 days, itraconazole oral solution 200 mg (which is equivalent to 20 ml) twice daily will be continued for a total of 14 days until clinically significant neutropenia is resolved.

Study Design

• Study Type: Observational
• Actual Enrollment: 203 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: The Relationship of Defeverscence and Itraconazole Plasma Level Using Sporanox IV as an Empiric Therapy in Immunocompromised Patients Who Have Been Treated With Sporanox Oral Solution as Prophylaxis
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Itraconazole Participants who have been receiving itraconazole will be observed prospectively. Itraconazole will be administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, followed by itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia is recovered.

Drug: Itraconazole; Itraconazole will be administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, followed by itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia is recovered.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment [Day 5]

   Percentage of participants who achieved more than or equal to 1000 ng/ml level after administration of study treatment were reported. Plasma level of itraconazole was defined as the sum of itraconazole concentration (IC) and hydroxyitraconazole concentration (HIC).

Secondary Outcome Measures

1. Percentage of Participants With Deferevescence After Administration of Study Treatment [Day 0 up to Day 14]

   Defervescence was defined as fall of the body temperature below 38.0 degree Celsius (C) at least once after starting to receive the study treatment.

2. Mean Time to Defervescence in Participants Who Received the Study Treatment [Day 0 up to Day 14]

   The mean time to defervescence was reported in participants who received the study treatment. Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment.

3. Duration of Neutropenia [Day 0 up to Day 14]

   The duration of neutropenia was reported. Neutropenia was defined as neutrophil count less than or equal to (<=) 500 cells per cubic millimeter (cells/mm^3), or neutrophil count <=1000 cells/mm^3 and anticipated to decrease to <=500 cells/mm^3 within several days.

4. Absolute Neutrophil Count (ANC) [Baseline (Day 0)]

   The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.

5. Percentage of Participants With Defervescence by Plasma Level of Itraconazole [Day 5]

   Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment. Plasma level of itraconazole was defined as the sum of IC and HIC.

6. Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment [Day 5]

   Plasma level of itraconazole was defined as the sum of IC and HIC. The OSR was defined based on satisfaction of the following criteria: (1) participants if treated for baseline fungal infection, there was either eradication (removal of fungus in culture), or presumed eradication; no evidence in culture but appeared to be treated clinically, (2) absence of breakthrough fungal infection during the treatment and for 7 days after completing the treatment, (3) survival for 7 days after completing the treatment, (4) absence of early withdrawal due to adverse events or lack of efficacy, and (5) defervescence. The presence and absence of OS was reported.

7. Percentage of Participants With Baseline Fungal Infection [Baseline (Day 0)]

   Blood cultures (a laboratory test on a sample of blood) were assessed to identify fungus. Percentage of participants with presence or absence of fungus before starting the study drug were calculated.

8. Plasma Concentration of Itraconazole by Breakthrough Fungal Infection [Day 5]

   Plasma level of itraconazole was defined as the sum of IC and HIC. A breakthrough fungal infection was defined as any fungal infection that was diagnosed more than (>) 3 days on or during therapy or within 7 days after completion of therapy. Blood cultures were assessed to identify fungus.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Immunocompromised participants with neutropenic fever who have been treated with itraconazole oral solution as prophylaxis

• Female participants who are postmenopausal or received contraceptive operation or refrain from sexual relations and women of childbearing potential should conduct an effective method of birth control (oral contraceptives, injections, intrauterine device, double barrier method, contraceptive patch and male partner's sterilization) before participation and during the study

• Male participants who will not have a baby within 2 months after the completion of itraconazole therapy

Exclusion Criteria:

• Fever due to documented deep-seated fungal infection at the entry into the study, but documented candidemia will be included

• Participants with kidney function related abnormalities with calculated creatinine clearance of 30 milliliter per minute (mL/min) or lower

• Aminotransferase level 5 times or higher of normal limit and total bilirubin level 5 milliliter per deciliter (mL/dL) or higher due to hepatic dysfunction

• Participants with dementia (mental decline) related to head injury and hypoxic brain injury

• Participants with mental illness which may interfere with cooperation in treatment and monitoring condition of the clinical study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Janssen Korea, Ltd., Korea

Investigators

• Study Director: Janssen Korea, Ltd., Korea Clinical Trial, Janssen Korea, Ltd., Korea

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Korea, Ltd., Korea
• ClinicalTrials.gov Identifier: NCT01021683
• Other Study ID Numbers: CR016597; ITR-KOR-5085; ITRFUN4049
• First Posted: Nov 30, 2009
• Last Update Posted: Aug 12, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Janssen Korea, Ltd., Korea: Hematological neoplasms; Neutropenia; Fever; Itraconazole; Sporanox; Antifungal prophylaxis; Defeverscence
• Additional relevant MeSH terms: Hematologic Neoplasms; Neutropenia; Itraconazole

Study Results

Participant Flow

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Period Title: Overall Study
STARTED	203
COMPLETED	132
NOT COMPLETED	71

Baseline Characteristics

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Overall Participants	150
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.2 (15.0)
Sex: Female, Male (Count of Participants)
Female	65 43.3%
Male	85 56.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment
Description	Percentage of participants who achieved more than or equal to 1000 ng/ml level after administration of study treatment were reported. Plasma level of itraconazole was defined as the sum of itraconazole concentration (IC) and hydroxyitraconazole concentration (HIC).
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	150
Number (95% Confidence Interval) [Percentage of Participants]	68.0 45.3%

2. Secondary Outcome

Title	Percentage of Participants With Deferevescence After Administration of Study Treatment
Description	Defervescence was defined as fall of the body temperature below 38.0 degree Celsius (C) at least once after starting to receive the study treatment.
Time Frame	Day 0 up to Day 14

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	150
Number [Percentage of Participants]	87.3 58.2%

3. Secondary Outcome

Title	Mean Time to Defervescence in Participants Who Received the Study Treatment
Description	The mean time to defervescence was reported in participants who received the study treatment. Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment.
Time Frame	Day 0 up to Day 14

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	131
Mean (Standard Deviation) [Days]	3.14 (1.57)

4. Secondary Outcome

Title	Duration of Neutropenia
Description	The duration of neutropenia was reported. Neutropenia was defined as neutrophil count less than or equal to (<=) 500 cells per cubic millimeter (cells/mm^3), or neutrophil count <=1000 cells/mm^3 and anticipated to decrease to <=500 cells/mm^3 within several days.
Time Frame	Day 0 up to Day 14

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	150
Mean (Standard Deviation) [Days]	2.64 (1.96)

5. Secondary Outcome

Title	Absolute Neutrophil Count (ANC)
Description	The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.
Time Frame	Baseline (Day 0)

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	148
Mean (Standard Deviation) [Cells/mm^3]	56.26 (127.91)

6. Secondary Outcome

Title	Percentage of Participants With Defervescence by Plasma Level of Itraconazole
Description	Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment. Plasma level of itraconazole was defined as the sum of IC and HIC.
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'n' signifies participants who were evaluable for this measure at given time points.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	150
IC+HIC < 1000ng/mL (n=48)	70.8 47.2%
IC+HIC >= 1000ng/mL (n=102)	95.1 63.4%

7. Secondary Outcome

Title	Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment
Description	Plasma level of itraconazole was defined as the sum of IC and HIC. The OSR was defined based on satisfaction of the following criteria: (1) participants if treated for baseline fungal infection, there was either eradication (removal of fungus in culture), or presumed eradication; no evidence in culture but appeared to be treated clinically, (2) absence of breakthrough fungal infection during the treatment and for 7 days after completing the treatment, (3) survival for 7 days after completing the treatment, (4) absence of early withdrawal due to adverse events or lack of efficacy, and (5) defervescence. The presence and absence of OS was reported.
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for given category.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	134
Presence of OS (n=95)	2328.10 (1612.00)
Absence of OS (n=39)	1690.90 (1185.20)

8. Secondary Outcome

Title	Percentage of Participants With Baseline Fungal Infection
Description	Blood cultures (a laboratory test on a sample of blood) were assessed to identify fungus. Percentage of participants with presence or absence of fungus before starting the study drug were calculated.
Time Frame	Baseline (Day 0)

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	150
Number [Percentage of Participants]	5.3 (1185.20) 3.5%

9. Secondary Outcome

Title	Plasma Concentration of Itraconazole by Breakthrough Fungal Infection
Description	Plasma level of itraconazole was defined as the sum of IC and HIC. A breakthrough fungal infection was defined as any fungal infection that was diagnosed more than (>) 3 days on or during therapy or within 7 days after completion of therapy. Blood cultures were assessed to identify fungus.
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for given category.

Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
Measure Participants	134
Presence of Breakthrough Fungal infection (n=128)	2155.70 (1529.20)
Absence of Breakthrough Fungal infection (n=6)	1864.20 (1509.80)

Adverse Events

Time Frame	Day 1 up to Day 14
Arm/Group Title	Itraconazole
Arm/Group Description	Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.
All Cause Mortality
	Itraconazole
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Itraconazole
	Affected / at Risk (%)	# Events
Total	28/203 (13.8%)
Cardiac disorders
Cardiac arrest	1/203 (0.5%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/203 (0.5%)
Hematemesis	1/203 (0.5%)
General disorders
Disease progression	1/203 (0.5%)
Multi-organ failure	1/203 (0.5%)
Infections and infestations
Bacterial sepsis	1/203 (0.5%)
Lung abscess	1/203 (0.5%)
Neutropenic sepsis	1/203 (0.5%)
Pneumonia	6/203 (3%)
Sepsis	6/203 (3%)
Septic shock	5/203 (2.5%)
Renal and urinary disorders
Pneumonia aspiration	1/203 (0.5%)
Renal failure acute	2/203 (1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/203 (0.5%)
Pulmonary edema	1/203 (0.5%)
Vascular disorders
Embolism	1/203 (0.5%)
Other (Not Including Serious) Adverse Events
	Itraconazole
	Affected / at Risk (%)	# Events
Total	49/203 (24.1%)
Blood and lymphatic system disorders
Thrombocytopenia	1/203 (0.5%)
Neutropenia	1/203 (0.5%)
Cardiac disorders
Arrhythmia	2/203 (1%)
Tachycardia	2/203 (1%)
Atrial fibrillation	1/203 (0.5%)
Gastrointestinal disorders
Diarrhoea	8/203 (3.9%)
Abdominal distension	3/203 (1.5%)
Nausea	2/203 (1%)
Abdominal pain	1/203 (0.5%)
Anal ulcer	1/203 (0.5%)
Constipation	1/203 (0.5%)
Dyspepsia	1/203 (0.5%)
Haematochezia	1/203 (0.5%)
Hemorroids	1/203 (0.5%)
Lip disorder	1/203 (0.5%)
Mouth ulceration	1/203 (0.5%)
Stomatitis	1/203 (0.5%)
Vomiting	1/203 (0.5%)
General disorders
Oedema peripheral	2/203 (1%)
Asthenia	1/203 (0.5%)
Oedema	1/203 (0.5%)
Pain	1/203 (0.5%)
Pyrexia	1/203 (0.5%)
Hepatobiliary disorders
Hyperbilirubinemia	4/203 (2%)
Infections and infestations
Pneumonia	3/203 (1.5%)
Bronchopneumonia	1/203 (0.5%)
H1N1 influenza	1/203 (0.5%)
Lung abscess	1/203 (0.5%)
Sepsis	1/203 (0.5%)
Sinusitis	1/203 (0.5%)
Streptococcal infection	1/203 (0.5%)
Investigations
Aspartate aminotransferase increased	5/203 (2.5%)
Alanine aminotransferase increased	4/203 (2%)
Blood alkaline phosphatase increased	2/203 (1%)
Blood bilirubin increased	1/203 (0.5%)
Blood lactate dehydrogenase increased	1/203 (0.5%)
Haemoglobin decreased	1/203 (0.5%)
Hepatic enzymes increased	1/203 (0.5%)
Liver function test abnormal	1/203 (0.5%)
Transaminases increased	1/203 (0.5%)
Metabolism and nutrition disorders
Hypokalaemia	2/203 (1%)
Decreased appetite	1/203 (0.5%)
Hyperkalaemia	1/203 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/203 (0.5%)
Back pain	1/203 (0.5%)
Flank pain	1/203 (0.5%)
Nervous system disorders
Headache	3/203 (1.5%)
Depressed level of consciousness	1/203 (0.5%)
Hypoaesthesia	1/203 (0.5%)
Psychiatric disorders
Disorientation	1/203 (0.5%)
Renal and urinary disorders
Anuria	1/203 (0.5%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/203 (0.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/203 (2.5%)
Epistaxis	2/203 (1%)
Acute respiratory distress syndrome	1/203 (0.5%)
Cough	1/203 (0.5%)
Productive cough	1/203 (0.5%)
Skin and subcutaneous tissue disorders
Rash	2/203 (1%)
Decubitus ulcer	1/203 (0.5%)
Erythema	1/203 (0.5%)
Pruritus	1/203 (0.5%)
Rash pruritic	1/203 (0.5%)
Vascular disorders
Hypotension	1/203 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI cannot provide any trial related information to external parties without mutual agreement with the Sponsor. This is valid even after the contract is cancelled.