IMPAACT 2034

IMPAACT 2034
Protocol Version 1.0, dated 15 July 2022

Laboratory Processing Chart, Version 1.1
LPC Edited/Updated: 12 Jul 2023
IMPAACT 2034 Laboratory Processing Chart
Phase I Study of the Pharmacokinetics, Safety, and Acceptability of a Single Dose of Pretomanid Added to an
Optimized Background Regimen in Children with Rifampicin-Resistant Tuberculosis
FOR USE WITH PROTOCOL VERSION 1.0 ONLY
Protocol Version and Date: 1.0, dated 15 Jul 2022 LPC Revised/Updated: 12 Jul 2023
Laboratory Technologists: Ibrahim Daud Email: Ibrahim.daud@usamru-k.org Phone: +254 797 383963
Laboratory Technologists: Dean K. Soko Email: dsoko@jhp.mw Phone: 265-888-898-947
Laboratory Data Manager: Sarah Wojcinski Email: wojcinski@frontierscience.org Phone: +1 716-834-0900 Ext. 7267
Laboratory Data Manager: Kevin Knowles Email: knowles@frontierscience.org Phone: +1 (716) 834-0900 ext. 7238
IMPAACT Lab Center Representative: Sara Zabih Email: szabih@milabcentral.org Phone: +1 (424) 946-5589
IMPAACT Lab Center Representative: Afton Dorasamy Email: adorasamy@milabcentral.org Phone: +1 (443) 972-0685
Westat Lab Center Representative: Lassallete Canada Email: LassalleteCanada@westat.com Phone: +1 (240) 314-2334
Protocol Questions: impaact.team2034@fstrf.org
Page 1 of 13
IMPAACT 2034
Table of Contents
Prioritization of Collection of Blood tubes and Processing for Short Draws ................................................................................................................................... 3
Protocol Required Non-Standard Reagents and Supplies ……………………………………………………………………………………………………………………………………………………...... 3
Section 1: Laboratory Schedule of Evaluations................................................................................................................................................................................. 4
Section 2: Safety and Clinical Laboratory Evaluations ...................................................................................................................................................................... 5
Section 3: Specimen Processing and Shipping Instructions .............................................................................................................................................................. 6
Section 4: Evaluations by Visit........................................................................................................................................................................................................... 7
Section 5: Helpful Links and Shipping Addresses............................................................................................................................................................................ 12
Section 6: Revision History .............................................................................................................................................................................................................. 13
Page 2 of 13
IMPAACT 2034
Prioritization of Collection of Blood tubes and Processing for Short Draws:

The IMPAACT 2034 team has adopted the NIH Guidelines for Limits of Blood Drawn for Research Purposes at the NIH Clinical Center for pediatric blood
collection. Collection will not exceed 5 mL/kg in a single day or a limit of 9.5 mL/kg in any 8-week period. Refer to the blood draw priority list below. All sites
should comply with local IRB limitations.
Visit Tube type Evaluation
Screening NA Samples should be collected at different time points throughout the allowable
screening window.
Day 0 (Entry) through Week 2 Spray dried K2 or K3 EDTA PK samples
SST/NON Chemistries
K2 or K3 EDTA CBC with differential and platelets
Protocol Required Non-Standard Reagents and Supplies

Unusual reagents or supplies required for unusual procedures
Evaluation Reagent or supply Order information
Greiner Vacuette 1. K2EDTA, 1 mL – Greiner Bio-One catalogue #454052 / Fisher Scientific Catalogue # 22-040-452
Intensive PK
1 mL K2 or K3 EDTA tube 2. K3EDTA, 1 mL – Greiner Bio-One catalogue #454034
Page 3 of 13
IMPAACT 2034
Section 1: Schedule of Evaluations
Study Visit Screening Day 0 Day 1 Day 2 Week 2

24 hours 48 hours
up to 28 days Day 14
Visit Window Entry post-dose post-dose
prior to Entry ±5 days
± 4 hours ± 4 hours
CLINICAL EVALUATIONS
Baseline medical and medication history X X
Interval medical and medication history X X X
Complete physical exam X X X X X
Pre- and
ECG X
~6-hrs post-dose
Study drug administration X
Palatability and acceptability assessment1 X
LABORATORY EVALUATIONS
Diagnostic HIV testing2 [if needed] [6 mL]
Pregnancy test3 [if needed] [X]
CBC with differential and platelets4 1 mL 1 mL 1 mL 1 mL
Chemistries4 3 mL 3 mL 3 mL 3 mL
Intensive PK sampling5 4 mL 1 mL 1 mL
Total Blood Volume 4-11 mL 8 mL 1 mL 5 mL 4 mL
1. Palatability and acceptability assessment should be conducted within approximately 30 minutes post-dose.
2. See Section 4.3 of the Protocol.
3. At screening, participants who have reached menarche or who are engaging in sexual activity (self-reported) must have a pregnancy test, with results
available prior to enrollment. Urine (5 mL) or blood (1 mL) tests are acceptable. The total blood volume shown above accommodates collection of 1
mL of blood, if needed.
4. CBC and chemistries are not required at the Day 0 (Entry) Visit if screening labs were drawn within 3 days. A smaller blood volume of 2 mL may
be collected at indicated visits for chemistry evaluations for participants who are less than one year of age.
5. Intensive PK sampling will be done as indicated in Table 8 at Day 0 (1, 3, 6, 9 hours post-dose), Day 1 (24 hours post-dose), and Day 2 (48 hours
post-dose). The blood volume per sample is 1 mL.
Page 4 of 13
IMPAACT 2034
Section 2: Safety and Clinical Laboratory Evaluations
Safety and Clinical Laboratory Evaluations

Defer to local clinical specimen collection guidelines for tube types and collection volumes whenever discrepancies occur.
Evaluation Tests eCRF #
Documentation of Samples tested to determine HIV status must be whole blood, serum, or plasma. HIV testing methods and LBW10052
HIV-1 algorithms must be approved for each site by the IMPAACT Laboratory Center (for NIAID-funded and protocol-
specific sites) or Westat (for NICHD-funded sites). Testing methods should be FDA-approved, if available. See
Protocol Section 4.3 for more details.
Hematology CBC with differential and platelets LBW10002
Chemistry Liver Function Tests: Total Bilirubin, *Indirect Bilirubin, Direct Bilirubin, Alkaline phosphatase, AST, ALT and LBW10002
Albumin
*Note: Indirect bilirubin may be calculated by clinic or laboratory staff, based on total and direct bilirubin results.
Electrolytes: Sodium, Potassium, Bicarbonate and Chloride
General Chemistry: Glucose, Calcium, Blood urea nitrogen, Creatinine, Total protein, Lipase and *eGFR
*Note: Estimated glomerular filtration rate (eGFR) may be calculated by clinic or laboratory staff, based on
creatinine results, using the Bedside Schwartz formula.
Pregnancy Testing Urine or Serum bHCG (pregnancy test) LBW10005

Test used must have sensitivity of 25mIU/mL or less.
Page 5 of 13
IMPAACT 2034
Section 3: Processing and Shipping Instructions
Specimen Processing and Shipping Instructions

CRF #
Evaluation Tube Type Special Collection Notes Processing Shipping
DMC Test Code
Intensive PK Sampling Spray dried Only venous blood collection is PKW10133 Centrifuge at 1500 g for ten Batch ship to UCT
K3/K2 acceptable minutes at room temperature. (frozen on dry
Time Points: 1, 3, 6, EDTA ice), when
9, 24 and 48 hrs post- Invert tubes 8-10 times to ensure Aliquot and store 2 x 0.25 mL in instructed.
dose mixing of anticoagulant and blood screw-capped cryovials.
and process within 2 hours at
room temperature Freeze at -80°C (-70°C to -95°C)
Please note: For PK sampling, the

blood volumes listed in the SoE
will be needed based on the
assays planned for the study.
However, if the full blood volume
indicated may not be collected
(because of blood draw challenges
and/or because of more stringent
local volume requirements), sites
should aim to collect at least 0.5
mL whole blood to yield at least
two separate aliquots of 0.1 mL
plasma.
Page 6 of 13
IMPAACT 2034
Section 4: Evaluations by Visit
Screening Visit (Up to 28 days prior to Entry)

LDMS Preloads are available for this visit when using visit code 0 Scr
LDMS Preload/Quick-Add Template Name- N/A
Evaluation Specimen CRF Aliquots/Tests LDMS Storage, Shipping and Special Notes
Code
HIV Testing EDTA/SST LBW10052 N/A N/A Complete HIV testing as needed per protocol
(if needed) (up to 6.0 mL) Section 4.3.3
Hematology EDTA Blood LBW10002 CBC with differential and platelets N/A Send to local lab ambient
(1.0 mL)
Chemistry NON or SST LBW10002 Total bilirubin, *Indirect bilirubin, N/A Send to local lab ambient
(3.0 mL) direct bilirubin, alkaline
phosphatase, AST, ALT and albumin *Indirect bilirubin may be calculated by clinic or
laboratory staff, based on total and direct
Sodium, potassium, bicarbonate bilirubin results.
and chloride
*Estimated glomerular filtration rate (eGFR) may
Glucose, calcium, blood urea be calculated by clinic or laboratory staff, based
nitrogen, creatinine, *eGFR, total on creatinine results, using the Bedside Schwartz
protein, lipase formula.
Pregnancy Test Urine (5.0 mL) LBW10005 N/A N/A Send to local lab ambient
(if needed) or NON/SST
(1.0 mL)
Page 7 of 13
IMPAACT 2034
Day 0 Visit (Entry)

LDMS Preloads are available for this visit when using Visit Code = 0 Ent
LDMS Preload/Quick-Add Template Name- 2034 0 Entry Intensive PK
Evaluation Specimen CRF Aliquots/Tests LDMS Code Storage, Shipping and Special Notes
(1.0 mL)
(3.0 mL) Direct bilirubin, Alkaline
phosphatase, AST, ALT, and *Indirect bilirubin may be calculated by clinic or
Albumin laboratory staff, based on total and direct
bilirubin results.
Sodium, Potassium, Bicarbonate
and Chloride *Estimated glomerular filtration rate (eGFR)
may be calculated by clinic or laboratory staff,
Glucose, Calcium, Blood urea based on creatinine results, using the Bedside
nitrogen, Creatinine, *eGFR, Total Schwartz formula.
protein, Lipase
Intensive PK Spray dried PKW10133 2 x 0.25 mL per timepoint BLD/DPE/PL1 Adjust LDMS preload aliquot volume to reflect
Sampling K3/K2 EDTA actual volume.
(1, 3, 6, and 9 (1.0 mL per
hrs post-dose) time point; Store at -80°C (-70°C to -95°C) until instructed
4.0 mL total) to ship to UCT.
Page 8 of 13
IMPAACT 2034
Day 1 Visit (24 hours post-dose ± 4 hours)

LDMS Preloads are available for this visit when using Visit Code = 1 Day
LDMS Preload/Quick-Add Template Name- 2034 Day 1 Intensive PK
Intensive PK Spray dried PKW10133 2 x 0.25 mL BLD/DPE/PL1 Adjust LDMS preload aliquot volume to
Sampling K3/K2 EDTA reflect actual volume.
(24 hrs (1.0 mL)
post-dose) Store at -80°C (-70°C to -95°C) until instructed
to ship to UCT.
Page 9 of 13
IMPAACT 2034
Day 2 Visit (48 hours post-dose ± 4 hours)

LDMS Preload/Quick-Add Template Name- 2034 Day 2 Intensive PK
(1.0 mL)
Chemistry NON or SST LBW10002 Total bilirubin, *Indirect bilirubin, N/A *Indirect bilirubin may be calculated by clinic
(3.0 mL) direct bilirubin, alkaline or laboratory staff, based on total and direct
phosphatase, AST, ALT and bilirubin results.
albumin
*Estimated glomerular filtration rate (eGFR)
Sodium, potassium, bicarbonate may be calculated by clinic or laboratory staff,
and chloride based on creatinine results, using the Bedside
Schwartz formula.
Glucose, calcium, blood urea
nitrogen, creatinine, *eGFR, total Send to local lab ambient
protein, lipase
Intensive PK Spray dried PKW10133 2 x 0.25 mL BLD/DPE/PL1 Adjust LDMS preload aliquot volume to
Sampling K3/K2 EDTA reflect actual volume.
(48 hrs (1.0 mL)
post-dose) Store at -80°C (-70°C to -95°C) until instructed
to ship to UCT.
Page 10 of 13
IMPAACT 2034
Day 14 Visit (± 5 days)

LDMS Preload/Quick-Add Template Name- N/A
(1.0 mL)
(3.0 mL) direct bilirubin, alkaline
phosphatase, AST, ALT and *Indirect bilirubin may be calculated by clinic
albumin or laboratory staff, based on total and direct
bilirubin results.
Sodium, potassium, bicarbonate
and chloride *Estimated glomerular filtration rate (eGFR)
may be calculated by clinic or laboratory staff,
Glucose, calcium, blood urea based on creatinine results, using the Bedside
nitrogen, creatinine, *eGFR, total Schwartz formula.
protein, lipase
Page 11 of 13
IMPAACT 2034
Section 5: Helpful Links and Shipping Addresses
Helpful Links and Shipping Addresses

ACTG/IMPAACT Laboratory Manual, Shipping Information and other useful information: Ship Plasma Samples to UCT
http://www.hanc.info/labs/labresources/Pages/informationActgImpaactLabs.aspx - Include an LDMS shipping manifest
- Notify lab >48 hours in advance of pending shipment
Note: Please contact the laboratories prior to shipment to ensure they can receive the - Notify the receiving lab of shipment, include shipping
samples at the designated time. Do not ship until you receive approval from the receiving manifest, Courier, and Tracking #
lab. Ensure that all import permits are up to date and accurate prior to shipping samples. - Ship in order for UCT to receive during weekdays ONLY
INTENSIVE PK PLASMA SHIPPING ADDRESS

Lubbe Wiesner, PhD
Clinical PK Lab Director
Division of Pharmacology, Univ. of Cape Town
K50.30 Division of Clinical Pharmacology
Old Main Building, Groote Schuur Hospital
Observatory, 7925
Cape Town, South Africa
Contact persons: Sandra Castel / Shameema Witbooi

Sandra.Castel@uct.ac.za and Shameema.Witbooi@uct.ac.za
Phone: +27 21 650 1284
LDMS Lab 499
NB: All sites must have a valid Material Transfer agreement in place with UCT, as well as a valid import permit for shipping into South Africa (if applicable).
Page 12 of 13
IMPAACT 2034
Section 6: Revision History
Version Date Comments

(DD MMM YYYY)
1.0 02 Sep 2022 First implementation version
1.1 12 Jul 2023 Pg 1: Addition of Westat Lab Center Representative
Pg 3: Added notation regarding the NIH Guidelines for Limits of Blood
Drawn for Research Purposes
Pg 3: Revision of PK tube type: 1 ml K2/K3 EDTA tube instead of 0.25-0.5 ml
Pg 6: Updated the Special Collection notes and freezing temperature range
Pg 8: Updated Specimen collection and freezing temperature range
Pg 9 & 10: Updated freezing temperature range
Pg 13: Note added to clarify changes made to the document
Please Note: Version 1.1 of the Laboratory Processing Chart (LPC) was finalized after Version 2.0 of the LPC. This was because Version 2.0 incorporated
changes that applied to sites implementing Protocol Letter of Amendment #1 while also incorporating other key changes that apply under Protocol
Version 1.0. Version 1.1 of the LPC incorporates only those changes to the LPC that apply under Protocol Version 1.0.
Page 13 of 13

IMPAACT 2034 - LPC - v1.1 - 12jul23

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Protocol Version 1.0, dated 15 July 2022

IMPAACT 2034 Laboratory Processing Chart

FOR USE WITH PROTOCOL VERSION 1.0 ONLY

Laboratory Technologists: Dean K. Soko Email: dsoko@jhp.mw Phone: 265-888-898-947

Protocol Questions: impaact.team2034@fstrf.org

Prioritization of Collection of Blood tubes and Processing for Short Draws:

Protocol Required Non-Standard Reagents and Supplies

Section 1: Schedule of Evaluations

Study Visit Screening Day 0 Day 1 Day 2 Week 2

Section 2: Safety and Clinical Laboratory Evaluations

Safety and Clinical Laboratory Evaluations

Hematology CBC with differential and platelets LBW10002

Electrolytes: Sodium, Potassium, Bicarbonate and Chloride

Pregnancy Testing Urine or Serum bHCG (pregnancy test) LBW10005

Section 3: Processing and Shipping Instructions

Specimen Processing and Shipping Instructions

Please note: For PK sampling, the

Section 4: Evaluations by Visit

Screening Visit (Up to 28 days prior to Entry)

Day 0 Visit (Entry)

Day 1 Visit (24 hours post-dose ± 4 hours)

Day 2 Visit (48 hours post-dose ± 4 hours)

Day 14 Visit (± 5 days)

Section 5: Helpful Links and Shipping Addresses

Helpful Links and Shipping Addresses

INTENSIVE PK PLASMA SHIPPING ADDRESS

Contact persons: Sandra Castel / Shameema Witbooi

Section 6: Revision History

Version Date Comments

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